Page 3«..2345..1020..»

Healios K K : Joint Research with the Division of Regenerative Medicine, the Institute of Medical Science for Developing a Mass Production Method of…

By daniellenierenberg

April 1st, 2022

Company Name: Representative:

HEALIOS K.K.

Hardy TS Kagimoto, Chairman & CEO

(TSE Mothers Code: 4593)

Joint Research with the Division of Regenerative Medicine, the Institute of Medical Science for Developing a Mass Production Method of UDC Liver Buds

HEALIOS K.K. ("Healios") is currently developing a regenerative medicine treatment whereby liver organ buds created from iPS cells are injected into the liver and grown into functioning liver tissue, with the aim of improving or restoring the function of a damaged liver (development code: HLCL041). This treatment could potentially replace the need for an organ transplant for certain patients. Liver buds are created by co-culturing liver progenitor cells, which can differentiate into hepatocytes; MSCs, which have the ability to develop into various types of connective-tissues; and vascular endothelial cells, which form blood vessels. Healios has pursued research and generated data on functional assessments and quality standards for these component cells and the liver buds created from them, and it is also proceeding with the development of mass culturing and manufacturing methods.

In addition, as announced on October 20th, 2020, Healios established Universal Donor Cells ("UDCs")*, which are next-generation iPS cells created with gene-editing technology that have a reduced risk of immune rejection regardless of a patient's HLA type, and its proprietary clinical-grade UDC line. We are currently conducting research both internally and through joint collaborations with several institutions on new treatments for diseases for which there is no existing cure.

As part of these efforts, Healios is pleased to announce that it has entered into a joint research agreement with the Division of Regenerative Medicine (Prof. Hideki Taniguchi) of the Institute of Medical Science at the University of Tokyo, to advance HLCL041 utilizing UDCs. In this joint research, we plan to establish a new method for inducing differentiation of liver buds using UDCs and to develop a highly efficient and scalable cell culturing and mass manufacturing system.

For many diseases where the only effective treatment is an organ transplant, Healios believes that organ buds created from iPSCs, which have the potential to restore organ function, hold significant promise as an alternative to organ transplants and as a means to address the perennial shortage of organ donors.

This agreement does not have a material impact on our consolidated financial results for the current fiscal year. We will promptly make an announcement on any matter that requires disclosure in the future.

Outline of the Collaboration Partner

Name of the Collaborator: Division of Regenerative Medicine, The Institute of Medical Science Adress:4-6-1 Shirokanedai Minato-ku, Tokyo, 108-8639, Japan

Representative: Professor Taniguchi Hideki

* UDCs

UDCs are iPS cells created using gene-editing technology that allows them to avoid and / or reduce the body's immune rejection response. The production of Healios' UDCs involve the removal of certain HLA genes that elicit a rejection response, the introduction of an immunosuppression gene to improve immune evasion, and the addition of a suicide gene serving as a safety mechanism, each in an allogeneic iPS cell. This next-generation technology platform allows for the creation of regenerative medicine products with enhanced safety and a lower risk of immune rejection, while preserving the inherent ability of iPS cells to replicate themselves continuously and their pluripotency in differentiating into various other kinds of cells.

About the Division of Regenerative Medicine, The Institute of Medical Science:

Regenerative medicine is a challenging scientific field that is going to convert the pioneering knowledge of developmental biology and stem cell biology to clinical application. For patients with end-stage organ failure, organ transplantation is the only effective treatment; however, the paucity of transplantable organs hinders the application of this treatment for most patients. Recently, regenerative medicine with transplantable organs has attracted attention. Our laboratory is developing a novel therapeutic strategy to substitute organ transplantation. We have established novel organoid culture technologies to reconstruct human organs from stem cells, including human induced pluripotent stem cells (iPSCs), and we are going to realize transplantation of human liver primordia (liver buds [LBs]) generated from iPSCs for the treatment of liver diseases. https://stemcell-imsut.org/laboratory/?id=en#labo1

About Healios:

Healios is Japan's leading clinical stage biotechnology company harnessing the potential of stem cells for regenerative medicine. It aims to offer new therapies for patients suffering from diseases without effective treatment options. Healios is a pioneer in the development of regenerative medicines in Japan, where it has established a proprietary, gene-edited "universal donor" induced pluripotent stem cell (iPSC) line to develop next generation regenerative treatments in immuno-oncology, ophthalmology, liver diseases, and other areas of severe unmet medical need. Healios' lead iPSC-derived cell therapy candidate, HLCN061, is a next generation NK cell treatment for solid tumors that has been functionally enhanced through gene-editing. Its near-term pipeline includes the somatic stem cell product HLCM051, which is currently being evaluated in Japan in Phase 2/3 and Phase 2 trials in ischemic stroke and acute respiratory distress syndrome (ARDS), respectively. Healios was established in 2011 and has been listed on the Tokyo Stock Exchange since 2015 (TSE Mothers: 4593). https://www.healios.co.jp/en .

Contact:

Department of Corporate Communications, HEALIOS K.K.

E-mail:ir@healios.jp

Go here to see the original:
Healios K K : Joint Research with the Division of Regenerative Medicine, the Institute of Medical Science for Developing a Mass Production Method of...

To Read More: Healios K K : Joint Research with the Division of Regenerative Medicine, the Institute of Medical Science for Developing a Mass Production Method of…
categoriaIPS Cell Therapy commentoComments Off on Healios K K : Joint Research with the Division of Regenerative Medicine, the Institute of Medical Science for Developing a Mass Production Method of… | dataApril 3rd, 2022
Read All

A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy

By daniellenierenberg

Theranostics. 2020; 10(8): 36223635.

Institute of Molecular and Cell Biology, 61 Biopolis Drive, 138673, Singapore

Competing Interests: The authors have declared that no competing interest exists.

Received 2019 Oct 4; Accepted 2019 Dec 20.

The transcriptional co-regulators YAP and TAZ pair primarily with the TEAD family of transcription factors to elicit a gene expression signature that plays a prominent role in cancer development, progression and metastasis. YAP and TAZ endow cells with various oncogenic traits such that they sustain proliferation, inhibit apoptosis, maintain stemness, respond to mechanical stimuli, engineer metabolism, promote angiogenesis, suppress immune response and develop resistance to therapies. Therefore, inhibiting YAP/TAZ- TEAD is an attractive and viable option for novel cancer therapy. It is exciting to know that many drugs already in the clinic restrict YAP/TAZ activities and several novel YAP/TAZ inhibitors are currently under development. We have classified YAP/TAZ-inhibiting drugs into three groups. Group I drugs act on the upstream regulators that are stimulators of YAP/TAZ activities. Many of the Group I drugs have the potential to be repurposed as YAP/TAZ indirect inhibitors to treat various solid cancers. Group II modalities act directly on YAP/TAZ or TEADs and disrupt their interaction; targeting TEADs has emerged as a novel option to inhibit YAP/TAZ, as TEADs are major mediators of their oncogenic programs. TEADs can also be leveraged on using small molecules to activate YAP/TAZ-dependent gene expression for use in regenerative medicine. Group III drugs focus on targeting one of the oncogenic downstream YAP/TAZ transcriptional target genes. With the right strategy and impetus, it is not far-fetched to expect a repurposed group I drug or a novel group II drug to combat YAP and TAZ in cancers in the near future.

Keywords: TEAD, YAP, TAZ, Hippo, cancer therapy

The transcriptional co-regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are key players that mediate various oncogenic processes and targeting their activities has emerged as an attractive option for potential cancer therapy. YAP, as the name suggests, was initially identified as a protein that associates with Yes, a src family kinase (SFK) 1. The exact function of YAP remained elusive until it was demonstrated to be a potent transcriptional activator 2. YAP's paralog TAZ, identified from a screen for 14-3-3 interacting proteins, is also a transcriptional co-activator 3 (Figure ).

The oncogenic milestones of the transcriptional co-regulators YAP and TAZ. Discovery of YAP/TAZ and TEAD functions predate the discovery of the Hippo pathway. Role of YAP/TAZ in the Hippo pathway and the discovery of their oncogenic abilities in cell and animal models are considered significant. The initial studies from the groups that linked YAP/TAZ to oncogenic signaling pathway, stemness, actin cytoskeleton, fusion genes, drug resistance, metabolism, angiogenesis and immune suppression are also listed.

YAP and TAZ do not have a DNA-binding domain and they need to associate with a transcription factor in order to access DNA. It has now emerged that YAP/TAZ use predominantly the TEAD (TEA domain) family of transcription factors 4 to elicit most of their biologically relevant gene expression programs. ChIP-Seq data unraveled a significant overlap in YAP/TAZ and TEAD peaks throughout the genome, and also showed that some YAP/TAZ-responsive genes are also synergistically regulated by AP-1 transcription factors 5, 6. In addition to its interaction with TEADs, YAP/TAZ also communicates with the mediator complex and chromatin modeling enzymes like the methyltransferase and SWI/SNF complex to elicit changes in gene expression 7-9. YAP/TAZ also suppress gene expression and should be regarded as co-regulators rather than co-activators 10.

YAP/TAZ are now considered as effectors of a physiologically and pathologically important signaling pathway - popularly called the Hippo pathway 11. The Hippo pathway was initially identified in a genetic mosaic screen in Drosophila but the pathway components are evolutionarily conserved. It is now known that the primary function of the Hippo pathway is to suppress the activity of Yorkie - the Drosophila homolog of YAP 12. The Hippo pathway in mammals also inhibits YAP/TAZ through phosphorylation by the large tumor suppressor (LATS) family of Hippo core kinases 13, which leads to cytoplasmic sequestration via interaction with 14-3-3 proteins and/or degradation via ubiquitin proteasome pathway 14, 15.

YAP and TAZ were first shown to transform mammary epithelial cells 16, 17. The oncogenic role of YAP became apparent when it was shown to be a driver gene in a mouse model of liver cancer 18 (Figure ). In a conditional transgenic mouse model, YAP overexpression dramatically increases liver size and the mouse eventually develops hepatocellular carcinoma 19, 20. In addition to causing primary tumor growth, YAP also helps in the metastatic dissemination of tumor cells 21.

Over a decade of research has revealed that YAP/TAZ integrates the inputs of various oncogenic signaling pathways, such as EGFR, TGF, Wnt, PI3K, GPCR and KRAS. Through expression of the ligand AREG, YAP was first shown to communicate with the EGFR pathway 22 (Figure ). The genes regulated by YAP/TAZ collectively coordinate various oncogenic processes, such as stemness, mechanotransduction, drug resistance, metabolic reprogramming, angiogenesis and immune suppression (Figure ), many of which are considered to be cancer hallmarks 23.

YAP and TAZ regulate the expression of crucial transcription factors like Sox2, Nanog and Oct4 and are able to maintain pluripotency or stemness in human embryonic stem cells (ESCs) and in induced pluripotent stem (iPS) cells 24, 25 (Figure ). More specifically, TAZ has been shown to confer self- renewal and tumorigenic capabilities to cancer stem cells 26. Within the microenvironmental landscape of tissues, YAP/TAZ are increasingly recognized as mechanosensors that respond to extrinsic and cell-intrinsic mechanical cues. To this end, mechanical signals related to extracellular matrix (ECM) stiffness, cell morphology and cytoskeletal tension rely on YAP/TAZ for a mechano-activated transcriptional program 27-29. YAP/TAZ target genes, CTGF and CYR61, cause resistance to chemotherapy drugs like Taxol 30 and YAP/TAZ has emerged as a widely used alternate survival pathway that is adopted by drug-resistant cancer cells 31. YAP/TAZ activity is regulated by glucose metabolism and is connected to the activity of the central metabolic sensor AMP-activated protein kinase (AMPK) 32-35. YAP/TAZ reprograms glucose, nucleotide and amino acid metabolism in order to increase the supply of energy and nutrients to fuel cancer cells 36. Through expression of proangiogenic factors like VEGF and angiopoetin-2 37, 38, YAP is able to stimulate blood vessel growth to support tumor angiogenesis 39. YAP is also shown to recruit myeloid-derived suppressor cells in prostate cancers in order to maintain an immune suppressive environment 40. Active YAP also recruits M2 macrophages to evade immune clearance 41.

A TAZ fusion gene (TAZ-CAMTA1) alone, in the absence of any other chromosomal alteration or mutation, is sufficient to drive epithelioid hemangioendothelioma (EHE), a vascular sarcoma 42, 43. Furthermore, comprehensive analysis of human tumors across multiple cancer types from the TCGA database unraveled that YAP and TAZ are frequently amplified in squamous cell cancers in a mutually exclusive manner 44. In human cancers, there is also a good correlation between YAP/TAZ target gene signature and poor prognosis. To date, a proportion of every solid tumor type has been shown to possess aberrant YAP/TAZ activity. Further, many of the upstream Hippo components that negatively regulate YAP/TAZ are found inactivated across many cancer types 45. Thus, all of this paint a clear picture of the prominent role played by YAP and TAZ at the roots of cancers 46, 47.

There are more than fifty drugs that have been shown to inhibit YAP/TAZ activity 48, however, with the exception of verteporfin; none act directly on YAP/TAZ. The unstructured nature of YAP and TAZ renders them difficult to target using small molecules. Therefore, YAP/TAZ inhibition is achieved indirectly through targeting their stimulators or partners. In this review, we focus on small molecules, antibody and peptide-based drugs, as the majority of the drugs in the clinic belong to this class. Less attention is given to nucleotide-based molecules and to small molecule YAP/TAZ inhibitors whose targets are unknown. We classify the YAP/TAZ-inhibiting drugs into three groups with each group having its own combating strategy to counter YAP/TAZ activity (Figure ). Group I drugs target the upstream YAP/TAZ stimulators and enhance the LATS-dependent inhibitory phosphorylation of YAP/TAZ in order to restrain their transcriptional output. Group II drugs/candidates act directly on YAP/TAZ or TEAD and may either interfere with the formation of the YAP/TAZ-TEAD complex or inhibit TEADs directly and hence affect YAP/TAZ-TEAD transcriptional outcomes. Group III drugs' combat strategy is to target the oncogenic proteins that are transcriptionally upregulated by YAP and TAZ.

Classification ofYAP/TAZ-TEAD inhibiting drugs into three groups. Group I drugs (red font) act upstream and prevent the nuclear entry of YAP and TAZ, group I drug targets for potential pharmacological exploitation in order to generate repurposed YAP/TAZ-inhibiting drugs are circled. Group II drugs (green font) disrupt the formation of the YAP/TAZ-TEAD complex and they primarily bind to the TEAD family of transcription factors. Group Ill drugs (blue font) act on the downstream transcriptional targets in order to prevent YAP/TAZ-mediated oncogenicity.

Group I drugs target the upstream proteins (Figure ), inhibition of which culminates in the enhancement of the LATS-dependent inhibitory phosphorylation of YAP/TAZ 49, 50. However, some group I targets like SFKs 51-53, AMPK 33, 34 and phosphatases 54-56 act directly on YAP and TAZ and activate them. Majority of group I drugs are kinase inhibitors, in addition to restricting YAP/TAZ nuclear entry; they intriguingly promote TAZ, but not YAP degradation. A possible explanation for this is the presence of two phosphodegrons that render TAZ more prone to degradation 15. Some group I drugs, such as MEK/MAPK inhibitors 57, 58 and -secretase inhibitors (GSIs) 59 have the ability to actively reduce both YAP and TAZ levels. HDAC inhibitors however, reduce YAP, but not TAZ levels 60. Here, we have classified the group I drugs based on the nature of the drug target.

Drugs targeting the EGFR, GPCR, Integrin, VEGFR and adenylyl cyclase families as well as those targeting receptors like the -secretase complex and Agrin are shown to inhibit YAP/TAZ activity 51, 61-64.

YAP/TAZ exploits the transformative abilities of the ErbB receptors (EGFR family) to drive cell proliferation. By transcribing ErbB ligands, such as AREG 22, 65, TGF- 66, NRG1 67 as well as the ErbB receptors EGFR and ErbB3 67, YAP is able to activate ErbB signaling and promote tumorigenesis. Sustained EGFR signaling also disassembles the Hippo core complexes leading to an increased active pool of YAP/TAZ 68 that is ready to transcribe more ErbB ligands/receptors. Under these conditions, EGFR inhibitors like Erlotinib 22 and AG-1478 66 (Figure ) are able to act as YAP/TAZ inhibitors and may be used for EGFR-driven cancers requiring YAP/TAZ transcription.

Signaling from G-protein coupled receptors (GPCRs), transduced by the associated G subunit or by the G subunits, modulates YAP/TAZ activities 69. Inhibiting Gq/11 sub-type signaling, using losartan 70, or stimulating Gs sub-type, using dihydrexidine, has been shown to stimulate YAP inhibitory phosphorylation 69. Agonism of Gs has been recently exploited to facilitate YAP/TAZ inhibition that reverses fibrosis in mice 71. G inhibition using gallein has also been shown to restrict YAP/TAZ 72. Activating mutations in the Gq/11 types of GPCRs present in approximately 80% of the uveal melanoma patients generate an active pool of YAP 73, 74 but the signal transduction occurs via Trio-Rho/Rac signaling and not through the canonical Hippo pathway 74.

Integrin signaling negatively regulates the Hippo pathway complexes to drive YAP/TAZ activity 75, 76. Although blocking integrin activity using RGD peptides 63, cilengitide (cyclic RGD peptide) 77, function-blocking antibodies - BHA 2.1 76 and clone AIIB2 78 has been shown to increase YAP/ TAZ's inhibitory phosphorylation, disappointingly, the efficacy of integrin- blocking drugs against cancers has not been clinically proven 79. Interestingly, a function-blocking antibody against Agrin, an extrinsic stimulator of integrin signaling, abrogates YAP-dependent proliferation in mouse models 63, 80.

Among the kinase inhibitors tested in a biosensor screen for LATS activity, the VEGFR inhibitors are shown to potently activate LATS and thereby inhibit YAP and TAZ activity 81. Further, VEGFR2 signaling is also shown to induce actin cytoskeletal changes and promote YAP/TAZ activation 82. Therefore, VEGFR inhibitors like SU4312, Apatinib, Axitinib and pazopanib are able to inhibit the expression of YAP/TAZ-responsive genes in endothelial cells. But whether these drugs work as YAP/TAZ inhibitors in cancer cells remains to be seen.

Enhancing cyclic AMP (cAMP) levels using the adenylyl cyclase activator forskolin activates the LATS kinases through Protein kinase A (PKA) and Rho 69, therefore forskolin is also a YAP/TAZ inhibitor. cAMP is degraded by the cyclic nucleotide phosphodiesterases (PDE), the use of PDE inhibitors like theophylline, IBMX, ibudilast and rolipram also promotes YAP/TAZ-inhibitory phosphorylation 83, 84.

Notch and YAP/TAZ signaling are also closely linked, inhibiting notch activity by targeting the -secretase complex, either using DAPT or dibenzazepine has been shown to decrease YAP/TAZ expression levels in mouse livers and also reduce YAP activation and YAP-induced dysplasia in the intestine 20, 51, 59.

Integrin signaling activates focal adhesion kinase (FAK), SFK and integrin- linked kinase (ILK). Growth factor and GPCR signaling occurs through mitogen-activated protein kinase (MAPK) and phosphoinositide 3-OH kinase (PI3K) signaling. There is also significant crosstalk in the signaling from these membrane receptors. Given the availability of potent small molecule drugs targeting the downstream kinases, they are leveraged on to inhibit YAP or TAZ activities.

Members of downstream integrin signaling pathway including FAK, its counterpart PYK2, and ILK have emerged as negative regulators of the core Hippo pathway and thus activate YAP/TAZ. Membrane receptors, such as ErbB and GPCRs are unable to activate YAP upon genetic deletion of ILK. Therefore, pharmacological inhibition of ILK using a specific ILK inhibitor, QLT0267 potently inhibits YAP-dependent tumor growth in xenograft models 85. The FAK inhibitors PF-562271 and PF-573228 have also been shown to enhance the LATS-mediated inhibitory phosphorylation of YAP 63, 75. A multi-kinase inhibitor CT-707 that predominantly inhibits FAK, anaplastic lymphoma kinase (ALK) and PYK2 is able to render cancer cells vulnerable to hypoxia through YAP inhibition 86. Inhibiting PYK2 activity using the dual PYK2/FAK inhibitor PF431396 destabilizes TAZ and also inhibits YAP/TAZ activity in triple negative breast cancer cells 87.

The SFK member Src prevents the activation of LATS 75, 88, thereby relieves YAP/TAZ inhibition by LATS. Interestingly, SFKs, Src and YES are also shown to activate YAP through direct tyrosine phosphorylation 51-53. Treating cells with SFK inhibitors, such as Dasatinib, PP2, SU6656, AZD0530 and SKI-1 inactivates YAP 51-53, 75, 88. In -catenin-driven cancers, YES facilitates the formation of a tripartite complex comprising -catenin, YAP and TBX5 that drives cell survival and tumor growth 53, 89. The SFK inhibitor dasatinib also serves as YAP inhibitor in these cancers 53. Dasatinib, in addition to inhibiting SFKs may also potently inhibit PDGFR and Ephrin receptors, both of which are known to activate YAP/TAZ 90, 91. However, FAK and SFK inhibitors have shown very limited efficacy against solid tumors in clinical trials therefore their utility in YAP-driven cancers remains to be seen.

MEK (MAP kinase kinase) and YAP interact with each other and maintain transformed phenotypes in liver cancer cells 57. MEK inhibitors PD98059, U0126 and trametinib or MAPK inhibitors CAY10561 and {"type":"entrez-nucleotide","attrs":{"text":"FR180204","term_id":"258307209","term_text":"FR180204"}}FR180204 are able to trigger degradation of YAP in a Hippo-independent manner 57, 58. The finding that MEK inhibition causes YAP degradation is, however, difficult to reconcile if YAP and TAZ are shown to mediate resistance to the MEK inhibitor trametinib 92. The efficacy of trametinib is also being evaluated in EHE, a cancer that is caused by the TAZ-CAMTA1 fusion gene ({"type":"clinical-trial","attrs":{"text":"NCT03148275","term_id":"NCT03148275"}}NCT03148275).

PI3K inhibitors Wortmannin/LY294002 as well as the drug BX795, an inhibitor of its effector 3'-phosphoinositide-dependent kinase-1 (PDK1) prevents nuclear entry of YAP 68. PI3K is closely linked to the mammalian target of rapamycin (mTOR) pathway. mTOR inhibitors temsirolimus and MLN0128 have been shown to inhibit YAP activity in patients with idiopathic pulmonary fibrosis and in a mouse model of cholangiocarcinoma, respectively 93, 94. YAP levels in TSC1 mutant mouse could also be reduced by blocking mTOR using torin1 treatment that induces the autophagy-lysosomal pathway 95.

YAP/TAZ inhibition is an additional unexpected activity possessed by the few kinase inhibitors mentioned above. However, apart from YAP/TAZ inhibition, all other signaling events initiated by the target kinase are also shut down due to inhibitor treatment. If these signaling events are critical for cellular homeostasis, then, toxic side effects will outweigh clinical benefits and this cannot be uncoupled from YAP/TAZ inhibition. Therefore, kinase inhibitors that failed in the trials due to unacceptable toxcity or poor pharmacokinetics may not be repurposed as YAP/TAZ inhibitors in the clinic. Focus should be on the kinase inhibitors that are already in the clinic like EGFR, VEGFR, MEK, PI3K or mTOR inhibitors but efficacy needs to be proven in order to repurpose them as YAP/TAZ inhibitors. The kinase targeted by the inhibitor must activate YAP/TAZ in tumors, for the treatment to be efficacious and this restricts the use of kinase inhibitors to selective tumor types. Intriguingly, YAP/TAZ activation has emerged as a prominent survival strategy adapted by cancers that cause drug resistance to EGFR and its downstream MEK/MAPK inhibitors 31. In such scenarios, coupling a group II YAP/TAZ inhibitor with a EGFR pathway inhibitor might offer the intended treatment benefits.

The mevalonate pathway is essential for the biosynthesis of isoprenoids, cholesterol and steroid hormones. Statins as well as other mevalonate pathway inhibitors like zoledronic acid and GGTI-298 that target farnesyl pyrophosphate synthase and geranylgeranyltransferase, respectively are identified as drugs that restrict the nuclear entry of YAP and TAZ 96, 97. Studies have also shown that combining statins like simvastatin with the EGFR inhibitor gefitinib provides stronger anti-neoplastic effects 98. Atorvastatin and zoledronic acid have entered Phase II clinical trials in triple negative breast cancer to test if they improve the pathological complete response rates ({"type":"clinical-trial","attrs":{"text":"NCT03358017","term_id":"NCT03358017"}}NCT03358017).

Actin polymerization promotes YAP/TAZ nuclear localization and therefore, polymerization inhibitors like latrunculin A 27 and cytochalasin D 28, 29 inhibit YAP/TAZ. Myosin or myosin light-chain kinase inhibitors like blebbistatin and ML-7, respectively have a similar effect 27, 29. Interfering with the actomyosin cytoskeleton through other means, such as Rho inhibition (toxin C3 treatment), or by using Rho kinase inhibitors like Y27632 has also been shown to have an inhibitory effect on YAP/TAZ 27, 29. p21 activated kinase (PAK) family kinases are cytoskeletal regulators as well as Hippo inhibitors. The PAK allosteric inhibitor IPA3 prevents YAP's nuclear entry 63, 99, further, the PAK4 inhibitor PF-03758309 is also shown to reduce YAP levels 77.

YAP/TAZ inhibitory phosphorylation is dynamic and the protein phosphatases PP1 and PP2A are shown to associate with YAP/TAZ and aid in their dephosphorylation and activation. Inhibiting these phosphatases using okadaic acid or calyculin A increases YAP/TAZ phosphorylation and shifts YAP/TAZ to the cytoplasm 54-56. Some of the oncogenic functions of YAP/TAZ are also mediated by the protein-tyrosine phosphatase SHP2 100, therefore SHP2 inhibitors have also been shown to attenuate YAP/TAZ activity 101.

Cellular energy stress is closely linked with attenuation of YAP/TAZ activities 32. Drugs that enhance energy stress like the mitochondrial complex I inhibitors metformin and phenformin, enhance YAP/TAZ inhibitory phosphorylation, cytoplasmic localization and suppression of YAP/TAZ- mediated transcription 32. The energy stress induced by these drugs activates AMPK, which is shown to phosphorylate and stabilize AMOTL1 - a YAP/TAZ negative regulator 32. AMPK is also shown to directly phosphorylate and inactivate YAP by disrupting its interaction with TEADs 33, 34. Therefore, AMPK activators A769662 and AICAR (an AMP-mimetic) are YAP inhibitors 32-34.

Histone deacetylases (HDACs) are uniquely positioned to alter the transcription of target genes. Interestingly, HDAC inhibitors panobinostat, quisinostat, dacinostat, vorinostat and Trichostatin A transcriptionally repress the expression of YAP but not TAZ, and thereby reduce YAP-addicted tumorigenicity 60. Treatment of cholangiocarinoma cells with the HDAC inhibitor {"type":"entrez-nucleotide","attrs":{"text":"CG200745","term_id":"34091806","term_text":"CG200745"}}CG200745 is also shown to decrease YAP levels 102. Although HDAC inhibitors are used to treat hematological malignancies their efficacy in solid cancers is questionable, however, combining HDAC inhibitor panobinostat with BET (bromodomain and extra-terminal) inhibitor I-BET151 achieves more effective YAP inhibition 103. There is also a clinical trial designed to evaluate the efficacy of HDAC/BET inhibitor combination in solid tumors and determination of YAP expression level after drug treatment is used as one of the objectives ({"type":"clinical-trial","attrs":{"text":"NCT03925428","term_id":"NCT03925428"}}NCT03925428). The BET family protein BRD4 is a part of the YAP/TAZ-TEAD transcriptional complex and inhibiting BRD4 using BET inhibitor JQ1 inhibits YAP upregulation and YAP-mediated transcription in KRAS mutant cells 104.

Many group I drugs can potentially be repurposed to treat YAP/TAZ- driven cancers 105. Among the group I drugs, only statins, trametinib and HDAC/BET inhibitors are being evaluated in clinical trials to test if they act against YAP/TAZ. Our prediction is that group I drugs that facilitate YAP/ TAZ inhibitory phosphorylation as well as degradation will have greater success in combating YAP/TAZ in cancers as YAP/TAZ degradation prevents their reactivation through other mechanisms. Importantly, the repurposing of group I drugs would also allow YAP/TAZ and its target gene(s) expression-based stratification amongst cancer patients.

Modalities that target either the TEAD family of transcription factors or YAP/TAZ are classified under this group (Figure ). The majority of the modalities, with the exception of verteporfin 106, target TEADs and are therefore predicted to act in the nucleus. By pairing with the TEAD family of transcription factors, YAP and TAZ upregulate the expression of many oncoproteins. The C-terminus of all TEADs possesses the YAP/TAZ-binding domain. The partnership between YAP/TAZ and TEAD is essential for the initiation of transcriptional program to drive oncogenesis. YAP is no longer oncogenic when sequestered by a dominant negative TEAD that lacks the DNA-binding domain 106. Similarly, a naturally occurring DNA-binding deficient TEAD isoform is also able to inhibit YAP/TAZ-mediated oncogenicity 107. Therefore, directly inhibiting TEAD or preventing YAP/TAZ-TEAD interaction is a promising and most direct strategy that warrants special attention 108.

Disruptors, stabilizers and destabilizers/degraders. A preformed YAP/TAZ-TEAD complex prevents access to drugs that occupy either the TEADs' surface or the palmitate-binding pocket (PBP), however, unassembled TEADs are accessible to drugs. Majority of the known YAP/TEAD-binding compounds are disruptors as they prevent the formation of the YAP/TAZ-TEAD complex. Two other classes of TEAD-binding compounds are stabilizers and destabilizers/degraders. Stabilizers either stabilize TEAD expression levels or enhance the formation of the YAP/TAZ-TEAD complex. Destabilizers bind to TEADs' surface or PBP and reduce TEAD expression levels through in situ denaturation, degraders on the other hand direct TEADs for proteasomal degradation.

Group I drugs target the upstream YAP/TAZ-activating proteins like the EGFR, GPCR, Src, or Integrins. As there are so many upstream YAP/TAZ activators, group I drugs are vulnerable to oncogenic bypass where inhibition of one group I YAP/TAZ activator leads to selection of cancer cells that activate YAP/TAZ via another group I activator. Strategically, Group II drugs may address this issue by directly targeting YAP/TAZ or TEAD, the converging points for various pathways and also the effectors for oncogenic transcription. However, Group II targeting modalities are still at the exploratory stage and it remains to be seen whether it is feasible to develop a Group II modality that works in clinic. We also need to be mindful of the possible associated toxicities due to YAP/TAZ-TEAD inhibition 109.

Most of the reported Group II modalities are disruptors; they target YAP/TAZ or TEAD and prevent their binary interaction. However, in addition to disruptors, in the future, we predict the emergence two other classes of group II compounds that would act as TEAD stabilizers and destabilizers/degraders (Figure ).

A small molecule benzoporphyrin drug named Verteporfin (VP) was shown to have the ability to bind to YAP and disrupt the YAP-TEAD interaction 106. VP is also able to inhibit YAP-induced excessive cell proliferation in YAP- inducible transgenic mice and in NF2 (upstream Hippo pathway component) liver-specific knockout mouse models 106. Although we do not understand the molecular details of VP binding to YAP, it is still undoubtedly the most popular YAP inhibitor within the scientific community. However, we need to be cautious as some of the tumor-inhibitory effects of VP are reported to be YAP- independent 110, 111. VP is photosensitive and proteotoxic and there is a need for better derivatives. A VP derivative, a symmetric divinyldipyrrine was shown to inhibit YAP/TAZ-dependent transcription but it is not clear if the compound specifically binds to YAP 112.

YAP and TAZ bind on the TEADs' surface; Inventiva Pharma has identified several compounds with benzisothiazole-dioxide scaffold that bind to the TEADs' surface and disrupt the YAP/TAZ-TEAD interaction. These compounds are currently in the lead optimization stage and have the potential to treat malignant pleural mesothelioma as well as lung and breast cancers that are driven by YAP/TAZ 113.

YAP cyclic peptide (peptide 17) and cystine-dense peptide (TB1G1) are also disruptors of YAP/TAZ-TEAD interaction in vitro but they have poor cell-penetrating abilities 114, 115. Interestingly, a peptide derived from the co-regulator Vgll4 appears to have remarkable cell-penetrating abilities and inhibits YAP-mediated tumorigenesis in animal models 116. Vgll proteins, named Vgll1-4 in mammals, belong to another class of co-regulators that pair with TEADs in a structurally similar, and therefore, in a mutually exclusive manner with YAP and TAZ 117, 118.

We identified a novel druggable pocket in the center of the TEADs' YAP/TAZ- binding domain 119 that could be occupied by fenamate drugs. Palmitate was subsequently shown to occupy this pocket, hereafter referred to as the palmitate-binding pocket (PBP). TEAD palmitoylation is shown to be important for stability and for the interaction with YAP 120, 121. Although the fenamate drug flufenamic acid competes with palmitate for binding to TEAD, higher concentrations are needed for it to be effective and it is not a disruptor of the interaction between YAP/TAZ with TEADs 122. However, covalently linking the fenamate to TEAD, using a chloromethyl ketone substitution, enables it to disrupt the YAP-TEAD interaction 123. The non-fused tricyclic compounds identified by Vivace Therapeutics could also be considered as fenamate analogs but it remains to be seen if they function as disruptors 124. Through structure-based virtual screen, vinylsulfonamide derivatives were identified as compounds that bind to PBP 125. Optimization of these derivatives yielded DC-TEADin02 a covalent TEAD autopalmitoylation inhibitor with an IC50 value of 200 nM. Interestingly, DC-TEADin02 is able to inhibit TEAD activity without disrupting the YAP-TEAD interaction.

Palmitate, by occupying the PBP, allosterically modulates YAP's interaction with TEAD 121, therefore it is conceivable that there might be small molecules that occupy the PBP and allosterically disrupt YAP/TAZ's interaction with TEADs. To this end, Xu Wu's group has identified and patented several potent compounds with alkylthio-triazole scaffold as PBP- occupying compounds that prevent YAP-TEAD interaction in cells 126. Another potent TEAD inhibitor that occupies the PBP is the small molecule K-975 127. K-975 also disrupts the YAP-TAZ-TEAD interaction and displayed anti-tumorigenic properties in malignant pleural mesothelioma cell lines much akin to the loss of YAP. Although palmitate is covalently attached to TEAD, it is a reversible modification and addition of PBP-occupying small molecules reduce the cellular palmitoylation status of TEADs 126. Moreover, the palmitoyl group is also removed from TEADs by depalmitoylases 128.

Being predominantly unstructured, YAP and TAZ are difficult to target directly. However, TEADs offer two attractive ways for targeting, one is to directly block the YAP/TAZ-binding pocket on the TEADs' surface with small molecules or peptides, whilst the other is to leverage on the PBP and allosterically disrupt YAP/TAZ interaction or inhibit TEADs (Figure ). However, the molecular determinants that confer YAP/TAZ disrupting ability to PBP-occupying small molecules are not clear. We do not know why flufenamate and DC-TEADin02 are unable to disrupt YAP/TAZ-TEAD interaction, like chloromethyl fenamate, K-975 and compounds with alkylthio-triazole scaffold.

The PBP could also be leveraged to allosterically enhance YAP/TAZ-TEAD stability or interaction. This prediction is subject to the identification of small molecules that functionally mimic the ligand palmitate (Figure ). Compounds with such an ability will enhance TEAD-dependent transcription and may have therapeutic value for regenerative medicine where enhancement of YAP/TAZ- TEAD activity is needed to repair damaged tissues 129. We recently identified that quinolinols occupy the PBP, stabilize YAP/TAZ levels and upregulate TEAD-dependent transcription 130. Enhanced YAP/TAZ levels increase the pool of assembled YAP/TAZ complex and therefore quinolinols could be considered as stabilizers (Figure ).

We identified a few chemical scaffolds that have the ability to occupy the PBP and destabilize TEAD (unpublished results). Addition of these compounds unfolds the TEADs' YAP/TAZ-binding domain and we call these compounds destabilizers (Figure ). Degraders could be generated when potent and selective TEAD surface or PBP-occupying compounds are coupled to proteolysis targeting chimera (PROTAC) 131 to direct TEAD proteasomal degradation. Therefore, destabilizers aim to reduce the cellular concentration of TEADs through in situ unfolding and degraders reduce TEAD levels through proteasomal degradation. Reducing the levels of their interacting partners deprives YAP/TAZ of their ability to activate transcription.

Any TEAD-binding compounds (disruptors, stabilizers or destabilizers/degraders) can only access unbound TEADs, as binding of YAP and TAZ blocks both the surface and the palmitate-binding pockets (Figure ). After accessing unbound TEADs, the disruptors and destabilizers/degraders reduce, whereas the stabilizers enhance, the formation of the YAP/TAZ-TEAD complex.

YAP/TAZ-mediated tumor development is due to the collective action of the repertoire of proteins that are expressed under their influence. However, some proteins are able to drive oncogenesis much better than others and they vary depending on the solid tumor and context. Therefore, drugs against these downstream YAP/TAZ targets including metabolic enzymes, kinases, ligands and proteins, such as BCL-xL, FOXM1 and TG2 are also used to combat YAP/TAZ-mediated oncogenicity (Figure ).

TAZ-dependent expression of ALDH1A1 (aldehyde dehydrogenase) is shown to impart stemness and tumorigenic ability; inhibition of ALDH1A1 using A37 reverses this transformation 132. GOT1 - the aspartate transaminase induced by YAP/TAZ, confers glutamine dependency to breast cancer cells and targeting this metabolic vulnerability using aminooxyacetate (AOA) represses breast cancer cell proliferation 133. Targeting the YAP/TAZ transcriptional target cyclooxygenase 2 (COX-2) using celecoxib inhibits cell proliferation and tumorigenesis in NF2 mutant cells 134. Interestingly, a positive feedback is seen in hepatocellular carcinoma cell lines where COX-2 is also shown to increase the expression of YAP 135. Inhibiting COX-2 using NS398 stimulates LATS-dependent phosphorylation of TAZ 136.

In hepatocellular carcinoma, Axl kinase has been shown to be crucial for mediating several YAP-driven oncogenic functions like cell proliferation and invasion 137. Similarly, YAP-driven Axl expression has been implicated in the development of resistance against EGFR inhibitors in lung cancer and sensitivity could be restored through Axl inhibition using TP-0903 138. YAP is shown to upregulate the expression of the kinase NUAK2 139 that, in turn activates YAP/TAZ by inhibiting LATS. Specific pharmacological inhibition of NUAK2 using WZ400 shifts YAP/TAZ to the cytoplasm and reduces cancer cell proliferation 140.

In a mouse model of prostate adenocarcinoma, the YAP-TEAD complex promotes the expression of the chemokine ligand CXCL5 that facilitates myeloid-derived suppressor cells (MDSC) infiltration and adenocarcinoma progression. Administering CXCL5 neutralizing antibody, or blocking CXCL5 receptor using the inhibitor SB255002, inhibits MDSC migration and tumor burden 40. The notch ligand Jagged-1 that is upregulated by YAP/TAZ is crucial for liver tumorigenesis 59, 141. Treating liver tumor cells with Jagged-1 neutralizing antibody greatly reduces oncogenic traits. The levels of integrin ligands CTGF and CYR61 that are also YAP target genes, could be reduced using the cyclopeptide RA-V (deoxybouvardin) leading to a reduction of YAP- mediated tumorigenesis in mst1/2 (Hippo homolog) knockout mouse model 142. Although neutralizing CTGF (FG-3019/pamrevlumab) and CYR61 (093G9) antibodies are available, they have not been effectively used against YAP/TAZ-driven cancers.

YAP mediates drug resistance to RAF- and MEK-targeted therapies in BRAF V600E cells, in part through the expression of the anti-apoptotic protein BCL- xL. BCL-xL inhibition using navitoclax sensitizes these cells to targeted therapies 92.

YAP-mediated proliferation through its target gene FOXM1 could be prevented in sarcoma cell lines and mouse models through the administration of thiostrepton that reduces FOXM1 levels 143.

Transglutaminase 2 (TG2) - the multifunctional transamidase is a YAP/TAZ target gene that is important for cancer stem cell survival and for maintaining integrin expression. TG2 inhibition using NC9 dramatically reduces tumorigenicity 144, 145.

We are aware that many of these target proteins also act upstream and stimulate YAP/TAZ by forming a positive feedback but we would nevertheless consider them in this group and not as group I as their expression is influenced by the TEAD-binding motif and YAP/TAZ.

Although attractive, toxicity issues and the identification of responsive patient population could be challenges in the successful implementation of the YAP/TAZ inhibitors in the clinic. YAP/TAZ inhibition might elicit toxicity 146; homozygous disruption of YAP in mice causes embryonic lethality, whereas TAZ knockouts are viable 147-150. Tissue-specific deletions of YAP in the heart 151, lung 152 or kidney 153 cause hypoplasia, whereas YAP/TAZ deletion in the liver cause hepatomegaly and liver injury 154. Surprisingly, YAP/TAZ knockouts in the intestine are well tolerated with no apparent tissue defects 155. All of these suggest that YAP and TAZ are crucial for development. However, they appear to be dispensable for adult tissue homeostasis. In most adult tissues, under normal homeostasis, YAP/TAZ are found restricted to the cytoplasm and are activated primarily in response to injury to initiate tissue regeneration. Therefore, it is predictable that administration of a YAP/TAZ inhibitor may not elicit severe toxicity. However, given the dynamic shuttling of YAP/TAZ/Yorkie between nucleus and cytoplasm 156-158, it is feasible that they still have a role in normal tissue homeostasis. Fittingly, YAP has been identified to be important for podocyte homeostasis and its functional inactivation compromises the glomerular filtration barrier and cause renal disease 109. Along similar lines, renal toxicity was observed in mice administered with K-975 - a YAP/TAZ-TEAD inhibitor 127. Renal toxicity in targeted therapy is very common and is seen in most of the kinase inhibitors used in oncology 159. Yet these kinase inhibitors are in the clinic as there is a therapeutic window, where the drug could be dosed to improve patient survival without causing much toxicity. The same could be envisaged for YAP/TAZ-inhibiting drugs.

Several drugs that act as YAP/TAZ inhibitors target multiple signaling pathways. Targeting multiple pathways could be a boon or a bane. Drug resistance is minimized in a multi-targeted approach as potential bypass mechanisms are also targeted. However, toxicity becomes an issue when the drug targets multiple important signaling pathways. For instance, raising cAMP through the use of PDE inhibitors activates a multitude of proteins like PKA, EPACs, ion channels and small GTPases. Similarly, GPCR modulators influence multiple pathways through signaling via G proteins, arrestins or GPCR kinases. To reduce toxic side effects, there are options available like selective targeting or biased signaling. Instead of hitting all the PDEs, the PDE enzyme that is the most potent activator of YAP/TAZ should be selectively targeted. Nonspecific PDE inhibitors cause more severe side effects than sub-type selective PDE inhibitors 160. Similarly, through stabilizing a particular GPCR conformation, certain small molecule GPCR modulators are able to effect signaling bias where one GPCR effector is preferentially activated over others, say G proteins over -arrestins, this way only a subset of signaling pathways get activated 161.

Another major challenge is the identification of patients responding to a YAP/TAZ inhibitor. YAP/TAZ expression is low in normal tissues and their levels are significantly elevated in cancers. Is YAP or TAZ positivity in tumors sufficient criteria to administer a YAP/TAZ inhibitor? YAP and TAZ might not be transcriptionally active or drivers in all tumors. Further, they could be expressing target genes that negatively regulate their activity 162, 163. There are also tumor types where YAP/TAZ or TEAD levels have no prognostic significance 46. These YAP/TAZ positive tumors are unlikely to respond to a YAP/TAZ inhibitor. Barring a few such scenarios, in many solid tumors, YAP or TAZ expression levels correlate well with higher-grade cancers or poor prognosis. Tumors with nuclear YAP or TAZ that are also positive for the downstream oncogenic YAP/TAZ target genes are likely to respond to a YAP/TAZ inhibitor and this should be used as criteria for patient stratification. As many of the YAP/TAZ-TEAD target genes are secreted proteins, the expression levels of these in the serum could also be estimated in addition to assessing their levels through immunohistochemistry.

As YAP and TAZ contribute to the acquisition of many hallmarks of cancer traits, targeting them is predicted to be more relevant for the management of several cancer types. It is still early to expect a newly developed drug against YAP/TAZ but it is nevertheless disconcerting to see that there are hardly any clinical trials that evaluate if known drugs could be repurposed as YAP/TAZ- inhibitors. Group I drugs are well suited to repurpose 105 but only statins ({"type":"clinical-trial","attrs":{"text":"NCT03358017","term_id":"NCT03358017"}}NCT03358017); trametinib ({"type":"clinical-trial","attrs":{"text":"NCT03148275","term_id":"NCT03148275"}}NCT03148275) and epigenetic modulators ({"type":"clinical-trial","attrs":{"text":"NCT03925428","term_id":"NCT03925428"}}NCT03925428) are being evaluated in clinical trials, assessment of the expression levels of YAP/TAZ after drug treatment is used as one of the clinical trial objectives. It is essential that we bolster our pharmacological arsenal so that we are prepared to combat YAP and TAZ. Group I drugs that failed in oncology trials are not expected to fare any better against YAP/TAZ. However, drugs that are already in the clinic like the kinase inhibitors targeting the EGFR or MEK, PDE inhibitors as well as GPCR modulators could be repurposed to combat YAP/TAZ. The cancer types need to be carefully stratified to ensure they are driven by YAP/TAZ through the upstream stimulator targeted by the drug. To overcome potential bypass mechanism or drug resistance, combinatory use of group I and II drugs could also serve as an avenue for cancer treatment. For the group III drugs, the situation may not be as promising, as they target only one of the many possible oncogenic proteins regulated by YAP/TAZ. Again, combinatory inhibition of few downstream target genes could be considered if they are collectively essential for oncogenic manifestation of YAP/TAZ-driven transcription. As they are new and untested, there is much excitement and progress in the development of novel group II compounds as drugs against YAP/TAZ. We are at an exciting juncture in the Hippo field where we could potentially see a novel group II drug or a repurposed group I drug to combat YAP/TAZ in the near future.

A.V. Pobbati and W. Hong are supported by the Agency for Science, Technology, and Research (A*STAR), Singapore. We thank Sayan Chakraborty, Gandhi T.K.B. and John Hellicar for critical reading of this review. We apologize to all authors whose work was not cited due to space constraints.

See the original post here:
A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy

To Read More: A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy
categoriaIPS Cell Therapy commentoComments Off on A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy | dataMarch 22nd, 2022
Read All

The Pipeline for of iPSC-Derived Cell Therapeutics in 2022 …

By daniellenierenberg

Despite progress involving the use of induced pluripotent stem cells (iPSCs) within disease modeling and drug discovery applications, it will be a long path to achieve the broad-scale use of iPSC-derived cell types in human patients.

Within a preclinical context, cell types differentiated from iPSCs are tested for their therapeutic response. Then, clinical trials are conducted to assure that essential parameters, such as tumorigenicity, dose toxicity, and immunogenicity, are assessed before authorizing the product for use in human patients. iPSC-derived cells have the potential to be used as therapies for treating cardiovascular, neurological, and metabolic diseases, as well as repairing damaged cartilage, spinal, motor neuron and eye tissues resulting from genetic defects or injuries.

In general, the targets for iPSC-derived therapies include any diseases or disorders for which there are no other viable treatments and where there is a need to repair or replace dysfunctional tissue.

Today, the following companies and organizations are forging the path toward iPSC-derived cell therapeutics.

While the groups above are involved with the development of iPSC-based cell therapeutics, not all of them have reached clinical-stage. Companies and organizations developing clinical-stage iPSC-derived therapeutics are described below.

In 2016, Cynata Therapeutics received a landmark approval to launch the worlds first formal clinical trial of an allogeneic iPSC-derived cell product (CYP-001) for the treatment of GvHD. In collaboration with Fujifilm, Cynata Therapeutics completed this Phase I trial in December 2018, reporting positive results.

Cynata Therapeutics is now testing its product candidate CYP-004 in a Phase 3 clinical trial enrolling up to 440 patients. CYP-004 is an allogeneic, iPSC-derived mesenchymal stem cell (MSC) product derived using Cynatas proprietary Cymerus technology. Led by the University of Sydney and funded by the Australian Government National Health and Medical Research Council (NHMRC), the trial will assess whether the cells can improve patient outcomes in osteoarthritis (OA).

It will be the worlds first clinical trial involving an iPSC-derived cell therapeutic to enter Phase 3 and the largest one ever completed.

In December 2019, the National Institutes of Health (NIH) announced it would be undertaking the first U.S. clinical trial of an iPSC-derived therapeutic. The goal of this trial is to restore dying cells of the retina. The Phase I/IIa clinical trial involves 12 patients with advanced-stage geographic atrophy who received an iPSC-derived retinal pigment epithelial (RPE) implant into a single eye. This trial is supported by the Ocular and Stem Cell Translational Research Section of the National Eye Institute (NEI). The NEI is part of the NIH.

In February 2019, allogeneic iPSC-derived NK cells produced by scientists from the University of Minnesota in collaboration with Fate Therapeutics were granted approval by FDA for a clinical trial. Specifically, Fate Therapeutics is exploring the clinical use of FT516 and FT500, which are its off-the-shelf, iPSC-derived natural killer (NK) cell product candidates. In December 2019, the company released promising clinical data from its Phase 1 studies.

In July 2020, Fate Therapeutics subsequently announced FDA clearance of its IND application for the worlds first iPSC-derived CAR T-cell therapy, FT819.FT819 is an off-the-shelf allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. Notably, the use of a clonal master iPSC line as the starting cell source will position Fate to mass produce CAR T-cells to be delivered off-the-shelf to patients.

The Japanese company Healios K.K. is preparing, in collaboration with Sumitomo Dainippon Pharma, for a clinical trial using allogeneic iPSC-derived retinal cells to treat age-related macular degeneration (AMD).

Of course, there are also numerous physician-led studies underway in Japan investigating the use of iPSC-derived cellular products inhuman patients. These clinical trials are for diseases such as macular degeneration, ischemic cardiomyopathy, Parkinsons disease, solid tumors, spinal cord injury (SCI) and platelet production.

Details on each of these Japanese trials are provided below:

Significant progress has been made for retinal degeneration diseases, particularly for age-related macular degeneration (AMD). In 2009, preclinical data showed for the first time the recovery of visual function in patients injected with retinal pigment epithelium (RPE) differentiated from iPSCs in a rat models retina. A major breakthrough was made when the group led by Masayo Takahashi at the Riken Centre for Developmental Biology in Japan produced iPSC-RPE cell sheets in 2014.

The above-mentioned successes led to the initiation of the first iPSCs clinical trial in 2014 itself. Scientists at the RIKEN Centre in Japan transplanted an autologous iPSC-RPE cell sheet just below the affected retina, without immunosuppression, in a 77-year-old woman with AMD. One year after the transplantation, the progression of the degeneration simply halted, an area with photoreceptors recovery was observed, and the patients vision remained stable. There were no symptoms of immune rejection or tumor development.

In March 2017, Japanese scientists announced that a 60-year-old man was the first patient to receive iPSC-RPE cells derived from another person (an allogeneic source). A clinical-grade iPSC bank for collecting and storing healthy HLA homozygous donors is now being established at the Centre for iPS Cell Research and Application (CiRA) in Kyoto (Japan).

Also in 2017, iPSC-derived cardiomyocytes were grafted on to a porcine model of ischemic cardiomyopathy by Kawamura, et al., using a cell-sheet technique. Cardiac function was significantly improved, and neovasculogenesis was observed. Recently, scientists from Osaka University were granted approval for a clinical trial to transplant allogeneic sheets of tissue derived from iPSCs onto the diseased hearts of three human patients.

Several preclinical studies in spinal cord injuries using iPSC-derived neural progenitor cells in animal models have provided evidence for remyelination and locomotor function recovery. In February 2018, the Japanese government gave an approval to Professor Hideyuki Okano for a clinical trial that will involve the treatment of patients with spinal cord injuries at Keio University.

In September 2018, group of scientists from Kyoto University were granted approval to begin a transfusion trial using platelets derived from iPSCs into an individual with aplastic anemia. The hope is that iPSC-derived platelets could replace transfusions of donated blood.

As early as 2008, it was confirmed that iPSC-derived dopaminergic neurons improved the symptoms and dopaminergic function of a rat model of Parkinsons disease. Approximately a decade later, in October 2018, dopamine precursor cells were created from allogeneic iPSCs produced by Jun Takahashis research group at Kyoto University. Physicians at Kyoto University Hospital then transplanted these cells into subjects with Parkinsons disease. A total of seven patients were involved.

In July 2019, scientists at Osaka University started a clinical trial for limbal stem cell deficiency, a condition in which corneal stem cells are lost. The scientists grafted a sheet of iPSC-derived corneal cells onto the cornea of a patient. Within one month, her vision seemed to have improved.

What questions do you have about the development of iPSC-derived cell therapeutics? Ask them in the comments below.

Read more:
The Pipeline for of iPSC-Derived Cell Therapeutics in 2022 ...

To Read More: The Pipeline for of iPSC-Derived Cell Therapeutics in 2022 …
categoriaIPS Cell Therapy commentoComments Off on The Pipeline for of iPSC-Derived Cell Therapeutics in 2022 … | dataMarch 22nd, 2022
Read All

Cell Therapy Processing Market CAGR of 27.80% Share, Scope, Stake, Trends, Industry Size, Sales & Revenue, Growth, Opportunities and Demand with…

By daniellenierenberg

Report Oceanpresents a new report onglobalcell therapy processing marketsize, share, growth, industry trends, and forecast 2030, covering various industry elements and growth trends helpful for predicting the markets future.

The global cell therapy processing market was valued at $1,695 million in 2018, and is projected to reach $12,062 million by 2026, registering a CAGR of 27.80% from 2019 to 2026.

Request Sample PDF of the Report https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

In order to produce a holistic assessment of the market, a variety of factors is considered, including demographics, business cycles, and microeconomic factors specific to the market under study. Global cell therapy processing market report 2021 also contains a comprehensive business analysis of the state of the business, which analyzes innovative ways for business growth and describes critical factors such as prime manufacturers, production value, key regions, and growth rate.

The Centers for Medicare and Medicaid Services report that US healthcare expenditures grew by 4.6% to US$ 3.8 trillion in 2019, or US$ 11,582 per person, and accounted for 17.7% of GDP. Also, the federal government accounted for 29.0% of the total health expenditures, followed by households (28.4%). State and local governments accounted for 16.1% of total health care expenditures, while other private revenues accounted for 7.5%.

Get our Request sample copy of the report:https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

This study aims to define market sizes and forecast the values for different segments and countries in the coming eight years. The study aims to include qualitative and quantitative perspectives about the industry within the regions and countries covered in the report. The report also outlines the significant factors, such as driving factors and challenges, that will determine the markets future growth.

Cell therapy is the administration of living cells to replace a missing cell type or to offer a continuous source of a necessary factor to achieve a truly meaningful therapeutic outcome. There are different forms of cell therapy, ranging from transplantation of cells derived from an individual patient or from another donor. The manufacturing process of cell therapy requires the use of different products such as cell lines and instruments. These cell therapies are used for the treatment of various diseases such as cardiovascular disease and neurological disorders.

Get a Request Sample PDF of the Report https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

Increase in the incidence of cardiovascular diseases, rise in the demand for chimeric antigen receptor (CAR) T cell therapy, increase in the R&D for the advancement in the research associated with cell therapy, increase in the potential of cell therapies in the treatment of diseases associated with lungs using stem cell therapies, and rise in understanding of the role of stem cells in inducing development of functional lung cells from both embryonic stem cells (ESCs) & induced pluripotent stem (iPS) cells are the key factors that fuel the growth of the cell therapy processing market.

Moreover, increase in a number of clinical studies relating to the development of cell therapy processing, rise in adoption of regenerative drug, introduction of novel technologies for cell therapy processing, increase in government investments for cell-based research, increase in number of GMP-certified production facilities, large number of oncology-oriented cell-based therapy clinical trials, and rise in the development of allogeneic cell therapy are other factors that augment the growth of the market. However, high-costs associated with the cell therapies, and bottlenecks experienced by manufacturers during commercialization of cell therapies are expected to hinder the growth of the market.

Request a free sample copy in PDF or view the report summary@https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

The cell therapy processing market is segmented into offering type, application, and region. By type, the market is categorized into products, services, and software. The application covered in the segment include cardiovascular devices, bone repair, neurological disorders, skeletal muscle repair, cancer, and others. On the basis of region, the market is analyzed across North America (U.S., Canada, and Mexico), Europe (Germany, France, UK, Italy, Spain, and rest of Europe), Asia-Pacific (Japan, China, India, and rest of Asia-Pacific), and LAMEA (Latin America, Middle East, and Africa).

KEY BENEFITS FOR STAKEHOLDERS The study provides an in-depth analysis of the market along with the current trends and future estimations to elucidate the imminent investment pockets. It offers a quantitative analysis from 2018 to 2026, which is expected to enable the stakeholders to capitalize on the prevailing market opportunities. A comprehensive analysis of all the geographical regions is provided to determine the existing opportunities. The profiles and growth strategies of the key players are thoroughly analyzed to understand the competitive outlook of the global market.

LIST OF KEY PLAYERS PROFILED IN THE REPORT Cell Therapies Pty Ltd Invitrx Inc. Lonza Ltd Merck & Co., Inc. (FloDesign Sonics) NantWorks, LLC Neurogeneration, Inc. Novartis AG Plasticell Ltd. Regeneus Ltd StemGenex, Inc.

LIST OF OTHER PLAYERS IN THE VALUE CHAIN (These players are not profiled in the report. The same will be included on request.) Beckman Coulter, Inc. Stemcell Technologies MiltenyiBiotec GmbH

Request To Download Sample of This Strategic Report:-https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

KEY MARKET SEGMENTSBy Offering Type Products Services Software

By Application Cardiovascular Devices Bone Repair Neurological Disorders Skeletal Muscle Repair Cancer Others

By Region North Americao U.S.o Canadao Mexico Europeo Germanyo Franceo UKo Italyo Spaino Rest of Europe Asia-Pacifico Japano Chinao Indiao Rest of Asia-Pacific LAMEAo Latin Americao Middle Easto Africa

Download Free Sample Report, SPECIAL OFFER (Avail an Up-to 2% discount on this report- https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

What are the aspects of this report that relate to regional analysis?

The reports geographical regions include North America, Europe, Asia Pacific, Latin America, the Middle East, and Africa.

The report provides a comprehensive analysis of market trends, including information on usage and consumption at the regional level.

Reports on the market include the growth rates of each region, which includes their countries, over the coming years.

How are the key players in the market assessed?

This report provides a comprehensive analysis of leading competitors in the market.

The report includes information about the key vendors in the market.

The report provides a complete overview of each company, including its profile, revenue generation, cost of goods, and products manufactured.

The report presents the facts and figures about market competitors, alongside the viewpoints of leading market players.

A market report includes details on recent market developments, mergers, and acquisitions involving the key players mentioned.

Following are the questions answered by the Market report:

What are the goals of the report?

This market report shows the projected market size for the cell therapy processing market at the end of the forecast period. The report also examines the historical and current market sizes.

On the basis of various indicators, the charts present the year-over-year growth (%) and compound annual growth rate (CAGR) for the given forecast period.

The report includes an overview of the market, its geographical scope, its segmentation, and the financial performance of key players.

The report examines the current state of the industry and the potential growth opportunities in North America, Asia Pacific, Europe, Latin America, and the Middle East, and Africa.

The research report includes various factors contributing to the markets growth.

The report analyzes the growth rate, market size, and market valuation for the forecast period.

For More Information or Query or Customization Before Buying, Visit @https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

What factors are taken into consideration when assessing the key market players?

The report analyzes companies across the globe in detail.

The report provides an overview of major vendors in the market, including key players.

Reports include information about each manufacturer, such as profiles, revenue, product pricing, and other pertinent information about the manufactured products.

This report includes a comparison of market competitors and a discussion of the standpoints of the major players.

Market reports provide information regarding recent developments, mergers, and acquisitions involving key players.

What are the key findings of the report?

This report provides comprehensive information on factors expected to influence the market growth and market share in the future.

The report offers the current state of the market and future prospects for various geographical regions.

This report provides both qualitative and quantitative information about the competitive landscape of the market.

Combined with Porters Five Forces analysis, it serves as SWOT analysis and competitive landscape analysis.

It provides an in-depth analysis of the market, highlighting its growth rates and opportunities for growth.

Access full Report Description, TOC, Table of Figure, Chart, etc. @https://reportocean.com/industry-verticals/sample-request?report_id=AMR714

Browse some more reports:

Veterinary Point of Care Blood Gas Analyzers Market

Orthodontics Market

Disposable medical gloves Market

Brain Health Supplements Market

Digital Wound Measurement Devices Market

Oral Proteins and Peptides Market

Hernia Repair Devices and Consumables Market

Disposable Gloves Market

Artificial Intelligence in Healthcare Market

Gene Therapy Market

Medical Computer Carts Market

Dental Chair Market

Medical Simulation Market

Clinical Trial Management (CTM) Market

Sinus Dilation Devices Market

Ventricular Assist Devices Market

About Report Ocean:We are the best market research reports provider in the industry. Report Ocean believes in providing quality reports to clients to meet the top line and bottom line goals which will boost your market share in todays competitive environment. Report Ocean is a one-stop solution for individuals, organizations, and industries that are looking for innovative market research reports.

Get in Touch with Us:Report Ocean:Email:sales@reportocean.comAddress: 500 N Michigan Ave, Suite 600, Chicago, Illinois 60611 UNITED STATESTel:+1 888 212 3539 (US TOLL FREE)Website:https://www.reportocean.com/

Here is the original post:
Cell Therapy Processing Market CAGR of 27.80% Share, Scope, Stake, Trends, Industry Size, Sales & Revenue, Growth, Opportunities and Demand with...

To Read More: Cell Therapy Processing Market CAGR of 27.80% Share, Scope, Stake, Trends, Industry Size, Sales & Revenue, Growth, Opportunities and Demand with…
categoriaIPS Cell Therapy commentoComments Off on Cell Therapy Processing Market CAGR of 27.80% Share, Scope, Stake, Trends, Industry Size, Sales & Revenue, Growth, Opportunities and Demand with… | dataJanuary 3rd, 2022
Read All

Stem cell therapy for diabetes – PubMed Central (PMC)

By daniellenierenberg

Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

Keywords: Embryonic stem cell, induced pluripotent stem cell, mesenchymal stem cell, diabetes

This lecture is based on a recent review.[1]

The increasing burden of diabetes worldwide is well-known, and the effects on health care costs and in human suffering, morbidity, and mortality will be primarily felt in the developing nations including India, China, and countries in Africa. New drugs are being developed at a rapid pace, and the last few years have seen several new classes of compounds for the treatment of diabetes e.g. glucagon-like peptide (GLP-1) mimetics, dipeptidyl-peptidase-4 (DPP-4) inhibitors, sodium glucose transporter-2 (SGLT2) inhibitors. New surgical treatments have also become increasingly available and advocated as effective therapies for diabetes. Gastric restriction surgery, gastric bypass surgery, simultaneous pancreas-kidney transplantation, pancreatic and islet transplantation have all been introduced in recent years. To avoid the trauma of a major operation, there have been many studies on the transplantation of isolated islets removed from a cadaveric pancreas. There was encouragement from the Edmonton protocol described by Shapiro and colleagues in the New England Journal in 2000. The islets were injected into the portal vein and patients, especially those suffering from dangerous, hypoglycemic unawareness, were treated before they had developed severe complications of diabetes, especially renal complications. While the early results were promising, with some 70% of the patients requiring no insulin injections after two years, at five years, most of these patients had deteriorated and required insulin supplements, despite some having received more than one transplant of islets. In the more recent series of patients, the Edmonton group has reported better long-term results with the use of the monoclonal anti-lymphocyte antibody, Campath 1H given as an induction agent, 45% of patients being insulin-independent at five years, and 75% had detectable C-peptide.

However, cadavaric pancreata and islets compete for the same source and are limited in number, and so, neither treatment could readily be offered to the vast majority of diabetic patients. Some have attempted to use an alternative source, for example, encapsulated islets from neonatal or adult pigs. This is still very experimental and will be a far away alternative with many technical and possibly ethical obstacles to overcome.

More recently, with the successes in the development of pluripotent adult stem cells (from Yamanaka, awarded the 2012 Nobel prize for medicine for developing induced pluripotent stem cells iPSCs), new approaches to seek a methods that may be more accessible and available have been attempted. Much hope was derived initially from embryonic stem cell (ESC) research, since these cells can be persuaded to multiply and develop into any tissue, but the process was expensive, and the problem of teratoma formation from these stem cells proved extremely difficult to overcome. Many of the important factors related to fetal development are not understood and cannot be reproduced. However, some progress has been made, and (occasionally) cells been persuaded to secrete insulin, but so far, there have been very minimal therapeutic application.

Scientists are now aware that to persuade a cell to produce insulin is only one step in what may be a long and difficult journey. Islets cells are highly specialized to have not only a basal release of insulin but also to respond rapidly to changes in blood glucose concentration. With insulin, the process and regulation of switching off secretion is as important as the switching on secretion.

A variety of approaches has been made with different starting points. The stem cell reproduces itself and can then also divide asymmetrically and form another cell type: This is known as differentiation. Although initially they were thought to be available only from embryos, non-embryonic stem cells can now be obtained without too much difficulty from neonatal tissue, umbilical cord, and also from a variety of adult tissues including bone marrow, skin, and fat. These stem cells can be expanded and made to differentiate, but their repertoire is restricted compared with embryonic stem cells: oligo- or pluri- as opposed to toti-potent embryonic stem cells. Even more, recently, there has been much interest in the process of direct cell trans-differentiation, in which a committed and fully differentiated cell, for example a liver cell, is changed directly to another cell type, for example an islet beta-cell, without induction of de-differentiation back to a stem cell stage.

Yamanaka, in 2006, was able to produce pluripotent stem cells from mouse neonatal and adult fibroblast cultures by adding a cocktail of four defined factors.[2] This led to a series of other studies developing the process, which was shown to be repeatable with human tissue as well as laboratory mice. The use of iPS cells avoided the ethical constraints of using human embryos, but there have been other problems and obstacles still. There have been emerging reports of iPS cells becoming antigenic to an autologous or isologous host, and the cells can accumulate DNA abnormalities and even retain epigenetic memory of the cell type of origin and thus have a tendency to revert back. Like embryonic stem cells, iPS cells can form teratoma, especially if differentiation is not complete.

Despite this, there has been very little success in directing differentiation of iPSCs to form islet beta-cells in sufficient quantity that will secrete and stop secretion in response to changes in blood glucose levels.

Another approach that has been tried is to combine gene therapy with stem cells. Some progress has been made in trying to express the desired insulin gene in more primitive undifferentiated cells by coaxing stem cells with differentiation factors in vitro and then by direct gene transfection using plasmids or a viral vector. We, and others, have used a human insulin gene construct and introduced ex vivo or in vivo into cells by direct electroporation (in ex vivo cells obviously) or by viral vectors. The adenovirus, adeno-associated virus, and various retro viruses have been most studied, especially the Lentivirus. However, any type of genetic engineering raises fears not only of infection from the virus but also of the unmasking of onco-genes, leading to malignancy, and there are strict regulations how to proceed to avoid these risks.

We have been interested in umbilical cord stem cells and in mesenchymal stem cells as targets for combined stem cell and gene therapy. These cells can be obtained in a reasonably easy and reproducible manner from otherwise discarded umbilical cord, or readily accessible bone marrow, selecting out the cells using various standard techniques. Fat, amnion, and umbilical cord blood are also sources, from which mesnechymal stem cells can be derived. After a proliferative phase, the cells take up an appearance similar to a carpet of fibroblasts, which can differentiate into bone, cartilage, or fat cells. Although mesenchymal stem cells from the various sources mentioned may look similar, their differentiation potentials are idiosyncratic and differ, which makes it inappropriate and difficult to think of them as a uniform source of target cells. Neonatal amnion cells and umbilical cord cells have low immunogenicity and do not express HLA class II antigens. They also secrete factors that inhibit immune reactions, for example, soluble HLA-G. Although immunogenicity is reduced significantly, they are still not autologous and, therefore, there remains a risk for allograft rejection. They have the advantage that they could be multiplied, frozen, and banked in large numbers and could be used in patients already needing immunosuppressive agents, for examples those having renal transplants.

In Singapore, our studies of umbilical cord-derived amnion cells have shown some success in having expression of insulin and glucagon genes, but little or no secretion of insulin in vitro. Together with insulin gene transfection in vitro, after peritoneal transplantation into sterptozotocin-induced diabetic mice, there was some improvement in glucose levels.[3] Our colleagues in Singapore[4,5] have used another model of autologous hepatocytes from streptozotocin-induced diabetic pigs. These separated hepatocytes were successfully transfected ex-vivo with a human insulin gene construct by electrophoration, and then the cells were injected directly back into the liver parenchyma using multiple separate injections. The pigs were cured of their diabetes for up to nine months - which is a remarkable achievement. As these were autotransplantations, no immunosuppressive drugs were necessary, but the liver cells were obtained from large open surgical biopsies. This necessity of surgical removal of liver tissue would limit its applicability, but nevertheless has been a good proof of concept study. In the context of autoimmune diabetes, the risk of recurrent disease may well persist unless the target of autoimmune attack could be defined and eliminated. In these porcine experiments, the human insulin gene with a glucose sensing promoter EGR-1 was used. There was no virus involved, and the plasmid does not integrate. Division of the transfected cell would dilute gene activity, but large numbers of plasmid can be produced cheaply. The same group of workers successfully transfected bone marrow mesenchymal stem cells with the human insulin gene plasmid using the same EGR-1 promoter and electrophoration. This cured diabetic mice after direct intra-hepatic and intra-peritoneal injection.

Finally, there should be caution in interpreting the results of these and other reports of cell and gene therapy for diabetes. In gene transfection and/or transplantation of insulin-producing cells or clusters in the diabetic rodent, there have been many reports in the literature, but only a few of these claims have been reproduced in independent laboratories. We have suggested the need to satisfy The Seven Pillars of Credibility as essential criteria in the evaluation of claims of success in the use of stem cell and/or gene therapy for diabetes.[1]

Cure of hyperglycemia

Response to glucose tolerance test

Evidence of appropriate C-peptide secretion

Weight gain

Prompt return of diabetes when the transfecting gene and/or insulin producing cells are removed

No islet regeneration of stereptozotocin-treated animals and no re-generation of pancreas in pancreatectomized animals

Presence of insulin storage granules in the treated cells

Here is the original post:
Stem cell therapy for diabetes - PubMed Central (PMC)

To Read More: Stem cell therapy for diabetes – PubMed Central (PMC)
categoriaIPS Cell Therapy commentoComments Off on Stem cell therapy for diabetes – PubMed Central (PMC) | dataNovember 22nd, 2021
Read All

Stem cells: Therapy, controversy, and research

By daniellenierenberg

Researchers have been looking for something that can help the body heal itself. Although studies are ongoing, stem cell research brings this notion of regenerative medicine a step closer. However, many of its ideas and concepts remain controversial. So, what are stem cells, and why are they so important?

Stem cells are cells that can develop into other types of cells. For example, they can become muscle or brain cells. They can also renew themselves by dividing, even after they have been inactive for a long time.

Stem cell research is helping scientists understand how an organism develops from a single cell and how healthy cells could be useful in replacing cells that are not working correctly in people and animals.

Researchers are now studying stem cells to see if they could help treat a variety of conditions that impact different body systems and parts.

This article looks at types of stem cells, their potential uses, and some ethical concerns about their use.

The human body requires many different types of cells to function, but it does not produce every cell type fully formed and ready to use.

Scientists call a stem cell an undifferentiated cell because it can become any cell. In contrast, a blood cell, for example, is a differentiated cell because it has already formed into a specific kind of cell.

The sections below look at some types of stem cells in more detail.

Scientists extract embryonic stem cells from unused embryos left over from in vitro fertilization procedures. They do this by taking the cells from the embryos at the blastocyst stage, which is the phase in development before the embryo implants in the uterus.

These cells are undifferentiated cells that divide and replicate. However, they are also able to differentiate into specific types of cells.

There are two main types of adult stem cells: those in developed bodily tissues and induced pluripotent stem (iPS) cells.

Developed bodily tissues such as organs, muscles, skin, and bone include some stem cells. These cells can typically become differentiated cells based on where they exist. For example, a brain stem cell can only become a brain cell.

On the other hand, scientists manipulate iPS cells to make them behave more like embryonic stem cells for use in regenerative medicine. After collecting the stem cells, scientists usually store them in liquid nitrogen for future use. However, researchers have not yet been able to turn these cells into any kind of bodily cell.

Scientists are researching how to use stem cells to regenerate or treat the human body.

The list of conditions that stem cell therapy could help treat may be endless. Among other things, it could include conditions such as Alzheimers disease, heart disease, diabetes, and rheumatoid arthritis. Doctors may also be able to use stem cells to treat injuries in the spinal cord or other parts of the body.

They may do this in several ways, including the following.

In some tissues, stem cells play an essential role in regeneration, as they can divide easily to replace dead cells. Scientists believe that knowing how stem cells work can help treat damaged tissue.

For instance, if someones heart contains damaged tissue, doctors might be able to stimulate healthy tissue to grow by transplanting laboratory-grown stem cells into the persons heart. This could cause the heart tissue to renew itself.

One study suggested that people with heart failure showed some improvement 2 years after a single-dose administration of stem cell therapy. However, the effect of stem cell therapy on the heart is still not fully clear, and research is still ongoing.

Another investigation suggested that stem cell therapies could be the basis of personalized diabetes treatment. In mice and laboratory-grown cultures, researchers successfully produced insulin-secreting cells from stem cells derived from the skin of people with type 1 diabetes.

Study author Jeffrey R. Millman an assistant professor of medicine and biomedical engineering at the Washington University School of Medicine in St. Louis, MO said, What were envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin.

Millman hopes that these stem cell-derived beta cells could be ready for research in humans within 35 years.

Stem cells could also have vast potential in developing other new therapies.

Another way that scientists could use stem cells is in developing and testing new drugs.

The type of stem cell that scientists commonly use for this purpose is the iPS cell. These are cells that have already undergone differentiation but which scientists have genetically reprogrammed using genetic manipulation, sometimes using viruses.

In theory, this allows iPS cells to divide and become any cell. In this way, they could act like undifferentiated stem cells.

For example, scientists want to grow differentiated cells from iPS cells to resemble cancer cells and use them to test anticancer drugs. This could be possible because conditions such as cancer, as well as some congenital disabilities, happen because cells divide abnormally.

However, more research is taking place to determine whether or not scientists really can turn iPS cells into any kind of differentiated cell and how they can use this process to help treat these conditions.

In recent years, clinics have opened that offer different types of stem cell treatments. One 2016 study counted 570 of these clinics in the United States alone. They appear to offer stem cell-based therapies for conditions ranging from sports injuries to cancer.

However, most stem cell therapies are still theoretical rather than evidence-based. For example, researchers are studying how to use stem cells from amniotic fluid which experts can save after an amniocentesis test to treat various conditions.

The Food and Drug Administration (FDA) does allow clinics to inject people with their own stem cells as long as the cells are intended to perform only their normal function.

Aside from that, however, the FDA has only approved the use of blood-forming stem cells known as hematopoietic progenitor cells. Doctors derive these from umbilical cord blood and use them to treat conditions that affect the production of blood. Currently, for example, a doctor can preserve blood from an umbilical cord after a babys birth to save for this purpose in the future.

The FDA lists specific approved stem cell products, such as cord blood, and the medical facilities that use them on its website. It also warns people to be wary of undergoing any unproven treatments because very few stem cell treatments have actually reached the earliest phase of a clinical trial.

Historically, the use of stem cells in medical research has been controversial. This is because when the therapeutic use of stem cells first came to the publics attention in the late 1990s, scientists were only deriving human stem cells from embryos.

Many people disagree with using human embryonic cells for medical research because extracting them means destroying the embryo. This creates complex issues, as people have different beliefs about what constitutes the start of human life.

For some people, life starts when a baby is born, while for others, it starts when an embryo develops into a fetus. Meanwhile, other people believe that human life begins at conception, so an embryo has the same moral status and rights as a human child.

Former U.S. president George W. Bush had strong antiabortion views. He believed that an embryo should be considered a life and not be used for scientific experiments. Bush banned government funding for human stem cell research in 2001, but former U.S. president Barack Obama then revoked this order. Former U.S. president Donald Trump and current U.S. president Joe Biden have also gone back and forth with legislation on this.

However, by 2006, researchers had already started using iPS cells. Scientists do not derive these stem cells from embryonic stem cells. As a result, this technique does not have the same ethical concerns. With this and other recent advances in stem cell technology, attitudes toward stem cell research are slowly beginning to change.

However, other concerns related to using iPS cells still exist. This includes ensuring that donors of biological material give proper consent to have iPS cells extracted and carefully designing any clinical studies.

Researchers also have some concerns that manipulating these cells as part of stem cell therapy could lead to the growth of cancerous tumors.

Although scientists need to do much more research before stem cell therapies can become part of regular medical practice, the science around stem cells is developing all the time.

Scientists still conduct embryonic stem cell research, but research into iPS cells could help reduce some of the ethical concerns around regenerative medicine. This could lead to much more personalized treatment for many conditions and the ability to regenerate parts of the human body.

Learn more about stem cells, where they come from, and their possible uses here.

Read the original:
Stem cells: Therapy, controversy, and research

To Read More: Stem cells: Therapy, controversy, and research
categoriaIPS Cell Therapy commentoComments Off on Stem cells: Therapy, controversy, and research | dataOctober 5th, 2021
Read All

How much does stem cell therapy cost in 2021? – The Niche

By daniellenierenberg

One of the most common questions Ive gotten over the last decade is, how much does stem cell therapy cost? They actually seem most often to want to know more specifically how much itshould cost.

To try to authoritatively answer this now in 2021 we need data from the present and past along with expert perspectives.

These kinds of questions on what are common and reasonable prices have continued in 2021. However, the types of queries have also evolved as things have gotten more complicated. There are many layers to the question of cost, which I cover here in todays article. In the big picture, the most worrisome potential cost is to your health if you proceed with unproven stem cell injections.

Stem cell cost questions | Stem cells cost $2,500 to $20,000| Why do stem cells cost so much? | How have stem cell prices changed? | Stem cell supplement cost | FTC actions and patients as consumers | Does insurance or Medicare cover stem cell therapy? | Patient fundraising | Looking ahead will stem cell costs go down?| References

This post is the most comprehensive look at stem cell treatment cost and costs of related therapies that Ive seen on the web, especially factoring in our inclusion of historical polling data from past years here on The Niche. The above bullet point list is what is covered in todays post and you can jump to sections that interest you most by clicking on those table of contents bullet points.

You can also watch the video I made summarizing the key points of this post below.

Furthermore, it encompasses other important issues related to insurance, fundraising, and approaches to being a smart consumer. Keep in mind that almost all stem cell therapies outside the bone marrow/hematopoietic sphere are not FDA-approved. They mostly lack rigorous data to back them up too. So this post is definitely not recommending you get them. I advise against it, but many people still want info on cost.

Lets get started.

After more than a decade of blogging about stem cells from just about every angle, its interesting to consider trends in the types of questions I get asked. Beyond cost, I also often get asked How much of a stem cell treatment price does insurance cover?

Of course, insurance (or lack thereof) directly bears on cost too. Ill get more into insurance later in the post.

In a way its not so surprising that cost is so much on peoples minds now for a few reasons.

First, as compared to many years back, people now view stem cell injections as a more everyday thing. Stem cell therapy is often available just down the street at a local strip mall.

Back in 2010 and in the 5 or so years after that, people instead more often viewed stem cells as some amazing thing out of reach to them at that time. Now people view stem cell offerings through the lens of consumers.

Sadly, another major part of the reason for the change in perceptions of stem cell treatments is the tidal wave of stem cell clinics from coast to coast in the US selling unproven and sometimes dangerous offerings.

At the same time, some universities and large medical centers also sell stem cell or similar offerings that arent proven. Im worried that that number may be increasing too and patients who may be paying there for unproven stem cells way at the very high end of the cost spectrum, sometimes above $100K.

Other stem cell suppliers and clinics market stem cell-related stuff that isnt real stem cells such as platelet rich plasma or PRP (see my comprehensive guide to PRP including a helpful infographic here) or injections of often dead perinatal stem cell products.

For all these reasons about once every year or two, I do polling asking the readers of The Niche here about their experiences.

Ive done the polling again now in 2020 in a more comprehensive form.

To have a sense of cost, we need to ask patients certain questions. How much did you pay per injection? How many injections did you get? Where did you get them?

Keep in mind that the total cost of stem cell therapy is the product of the cost per injection times the # of injections. For instance, if a stem cell injection costs $8,000 and you get 10 injections, your total cost is $80,000.

Unfortunately, the unproven stem cell clinics generally do not volunteer data on how much they charge. They also often encourage patients to get many injections.

Our 2020 polling data (you can still participate and I will update this) for stem cell treatments are in the graphic above. Here are some highlights.

The self-reported responses on cost for stem cell treatments, as indicated by respondents to our 2020 polling, suggest the price has gone up.

While the most common answer in 2019 was $2,501-$5,000, in 2020 the most common response was $10,001-$20,000, while $2,501-$5,000 was close behind.

The percentage of people paying the most, more than $100,000, was only slightly (probably non-significantly) higher in 2020, but both in 2019 and 2020 the percentage of people paying over $100K was much higher than in 2018 polling.

Keep in mind this is the cost per injection so how many injections do patients typically get? While the number of injections reported most commonly was 1 in both 2019 and 2020, in 2020, the second most common answer was 6-10 injections, a big boost from 2019. Again, more injections end up multiplying things up to boost the total cost. Only a few people in the polling had many injections, but in my view it is still striking to see anyone say theyve received more than 20 stem cell injections.

For comparison, the 2019 polling can be found here, but some of the key results are captured in a combo screenshot Ive included here. I got a lot more responses to the polling in 2019 so that makes me more confident in the data than in the 2020 polling so far, but I hope well get more responses moving forward in 2020 and if we do, again Ill update the info in this post.

What you can see from 2019 is that a plurality of respondents reported getting one stem cell injection, but 60% of people nonetheless got more than one stem cell injection.

Remarkably about 1 in 20-25 people received more than 20 stem cell injections.

About another 1 in 20 people got 6-20 injections. I find this amount of repeat injections to be surprising and concerning as it amplifies health and financial risks.

In terms of cost per injection, the results are pretty similar to 2018 (see at right below) on the whole.

This kind of polling isnt super scientific, but can gauge trends. Unfortunately, I havent really seen much other published data on stem cell clinic costs in actual journals.

I dont know if its noise or not, but the percentage of people paying over $100K is about 2-fold higher in 2019 versus 2018.

There are more people may be paying $10K-$20K as well now in 2020 vs. 2019 or 2018.

There is growing interest from the public in stem cell supplements. I did a post on this earlier in 2020 so take a look here, which was essentially a review of stem cell supplements like Regenokine. In terms of cost, while supplements are far less expensive than getting stem cell, PRP, or exosome injections, supplements are still pricey for what you get. Its not unusual to pay $100 for a small bottle of stem cell supplements, the other factor to consider is that these supplements generally have no solid, published data behind them so you might as well be paying $100 for water. Its unclear what risks taking these supplements might bring as well.

On the economic side, you might think that the feds like the FTC would be actively pursuing false or even fraudulent marketing of stem cells via the web and other kinds of advertising, but in total so far the FTC to my knowledge has only taken relatively few actions such as this one. and then some letters for COVID-related marketing of stem cells and other biologics earlier this year in 2020.

Oddly, there were just that a couple blips of FTC activity, especially considering the sea of questionable stem cell clinic-related ads out there. This ranges from major newspapers to inflight magazines to mobile ads on a stem-cell-mobile to television. Then of course there are the infomercial seminars.

Patients should also view themselves as consumers. Savvy customers considering paying money to stem cell clinics should do their homework. I often tell patients to use at a minimum the kinds of tough standards they bring to the car-buying process. Over the last few years Consumer Reports has been interested in the stem cell treatment world and done some reporting that is worth reading.

A common question I hear is the following: is stem cell therapy covered by insurance? Unfortunately for patients desperate to try stem cells, insurance generally does not provide any coverage, which often leads them to take extreme financial measures. These steps can include fundraising (more below).

In my view, the Regenexx brand has made a big deal out of how some employers contribute towards costs of their clinics offerings. Im not so clear on where that stands today in 2020.

Does Medicare cover stem cell therapies? Medicare will generally cover the cost of established bone marrow transplantation type therapies. However it does not cover unproven stem cell therapies.

Patients are often reaching out to me so I know that many of them have gone to extraordinary measures to raise the money to pay to unproven stem cell clinics. Its painful to think about what little they get in return. Since we are by definition talking about unproven medical procedures here, in my view this money is largely down the drain.

If you have other data on stem cell economic issues such as what patients pay please let me know. Then theres the issue of what it actually costs the clinics per injection and in turn: whats their profit margin?

What ends up happening is that patients take out second mortgages on their houses, try to collect funds from friends and relatives, or turn to online fundraising. The internet fundraising efforts most often end up on GoFundMe. This is a trend Ive been noticing for years. Some colleagues even published a paper on this trend, a very interesting and an important read. The paper is Crowdfunding for Unproven Stem CellBased Interventions in JAMA by Jeremy Snyder,Leigh Turner , and Valorie A. Crooks. Heres a key passage:

As of December 3, 2017, our search identified 408 campaigns (GoFundMe=358; YouCaring=50) seeking donations for stem cell interventions advertised by 50 individual businesses. These campaigns requested $7439308 and received pledges for $1450011 from 13050 donors. The campaigns were shared 111044 times on social media. Two campaigns were duplicated across platforms but shared separately on social media. Of the 408 campaigns, 178 (43.6%) made statements that were definitive or certain about the interventions efficacy, 124 (30.4%) made statements optimistic or hopeful about efficacy, 63 (15.4%) made statements of both kinds, and 43 (10.5%) did not make efficacy claims. All mentions of risks (n=36) claimed the intervention had low/no risks compared with alternative treatments.

Supposedly GoFundMe has taken some steps to lower the often ethically thorny stem cell fundraising on its site, but Im not sure how much it has changed.

There is pressure on stem cell clinics now in 2021 in large part due to two factors. These could drive costs down or up depending on how things play out. First, the FDA is much more active against unproven stem cell clinics. This may mean more money from the clinics going toward paying attorneys or FDA compliance experts. Youd think this might drive costs up. However, the still large number of clinics may keep pressure to stay with keeping price tags lower.

The second factor is the COVID-19 pandemic, which has forced many clinics to stop injections temporarily. While a surprising number of clinicsI did by phone were still open in a small informal survey, others were in a holding pattern. This may lower supply which could raise prices. But I think demand is likely way down as many patients stay home to avoid COVID risks. This could be temporary though. As things start re-opening, as they are now, the clinics may be able to capitalize on pent-up demand.

To sum up, the answer to the question, How do stem cells cost? is largely driven by clinic firms aiming to profit. Overall, clinics will charge what they think patients will pay them, which will always be a moving target. I urge patients to be cautious both medically, talking to their doctors, and financially.

Link:
How much does stem cell therapy cost in 2021? - The Niche

To Read More: How much does stem cell therapy cost in 2021? – The Niche
categoriaIPS Cell Therapy commentoComments Off on How much does stem cell therapy cost in 2021? – The Niche | dataOctober 5th, 2021
Read All

"Stem cell-based therapeutics poised to become mainstream option – BSA bureau

By daniellenierenberg

In conversation with Dr Koji Tanabe, Founder and CEO, I Peace, Inc., The United States/Japan

To make the trial investments more meaningful and to avoid ambivalence in animal models, medical science is adopting novel in vitro models of specialised human pluripotent cell lines. Pluripotent stem cells(PSCs) have the agility to expand indefinitely and differentiate into almost any organ-specific cell type. iPSC-derived organs andorganoidsare currently being evaluated in multiple medical research arena like drug development, toxicity testing, drug screening, drug repurposing, regenerative therapies, transgenic studies, disease modeling and more across clinical developments. Innovative pharmacovigilance methodologies are preferring induced pluripotent stem cells (iPSCs) for pre-clinical and clinical investigational studies. Global Induced Pluripotent Stem Cell (iPSC) market is expected to reach $2.3 B by 2026. The iPSC market inAsia-Pacificis estimated to witness fast growth due to increasing R&D projects across countries likeAustralia,JapanandSingapore.

I Peace, Inc. a Palo Alto-based global biotech company with its manufacturing base in Japan, has succeeded in developing and mass-producing clinical grade iPS cells through its proprietary iPS cell manufacturing services. The human iPSC (hiPSC) lines at I Peace leverage differentiated cells across clinical research and medical applications. Biopsectrum Asia discovered more about Japan's stem cell manufacturing ecosystem with Dr Koji Tanabe, Founder and CEO, I Peace, Inc., (The United States/Japan). Tanabe earned his doctorate under Dr Shinya Yamanaka, a Kyoto University researcher who received the 2012 Nobel Prize in Physiology or Medicine for discovery of reprogramming adult somatic cells to pluripotent cells. I Peace is focusing on this Nobel Prize-winning iPSCs technology where Tanabe had played a key role in generating the worlds first successful human iPSCs as one of the team members and is currently industrialising it in the US and Japan.

How do you define Japans Stem cell manufacturing dynamics aligning with regional and APAC market potential?

We believe that human cells play a pivotal role in next-generation drug therapy. Clinical trials of iPSC applications are in full swing not only in Japan, but worldwide as well. In the US, the momentum of clinical trial research is astounding. Yet, mass production of GMP compliant cell products remains a challenge. Entry into this venture is no easy task. As a contract development and manufacturing organisation (CDMO), I Peace is geared to tackle that challenge and become the pioneer of mass production technology of clinical grade cell products.

Can you elaborate I Peaces cost-effective proprietary stem cell synthesis solution and its manufacturing scale?

The key advantage of iPSCs is the ability to create pluripotent cells from an individuals own cells. Furthermore, iPSCs can multiply indefinitely and evolve into any type of cell, making iPSCs an ideal tool for transplant and regenerative medicine and drug research. However, clinical applications of iPSCs to date, utilise heterogenic transplantation. It is because manufacturing of just one line of iPSCs requires a cost intensive clean room to be occupied for several months. Manufacturing process complexities also pose a barrier to cost reduction and mass production.

In contrast, I Peace has developed a proprietary, fully automated closed system for iPS manufacturing, enabling cost-effective production of multiple lines of iPSCs from multiple donors in a single room. Within a few years, we expect to manufacture several thousand lines of iPSCs simultaneously in a single room. With this technology, I Peace can efficiently generate an ample supply of various iPSCs for heterogenic transplant, while also fostering a society where everyone can bank their own iPSCs for potential medical use.

How does I-Peace better position its businesses objectives and go-to-market strategies?

I Peaces manufacturing facility and its processes have undergone rigorous audits and are certified to be in compliance with GMP guidelines of the US, Japan, and Europe. We have the capacity to manufacture clinical-grade iPSCs and iPSC-derived cells for clinical use in the global market. Our manufacturing staff have unparalleled expertise in the manufacturing of iPSCs, and their knowledge and experience make it possible to mass produce high quality clinical-grade iPSCs in the shortest possible time. Additionally, we streamlined the iPSC use licensing scheme to expedite collaborative ventures with downstream partners. We believe these strategies position I Peace as a global leader in iPSC technology.

How do you outline the concept of democratising access to iPSC manufacturing?

At I Peace, we envision a world in which everyone would possess their own iPSCs and if needed, receive autologous transplant medication using their own iPSC. We believe in the importance of raising awareness of Nobel Prize winning iPSC technology and we think much more needs to be done. We need to enlighten the public about iPSCs - what they are, how they are created, and how they play a role in next-generation medical therapies. We also need to underscore the benefits of early banking ones own iPSCs, such as autologous transplant and the fact that cells taken in the early stages of life are preferable over cells collected later in life.

To democratise iPSC access, it is also important to expedite application research. We work closely with downstream partners, and support their iPSC-derived drug therapy development efforts by providing iPSCs to meet their needs. We also collaborate with downstream partners in the development of promising therapies including the use of T-cells for cancer therapy, cardiomyocytes for the treatment of heart disease, and neurocytes for neurological disease.

What is your outlook around boosting public-private stakeholders initiatives to encourage awareness on stem-cell-based therapeutics?

iPSC research has advanced tremendously over the past 16 years, and even more so since Dr Shinya Yamanakas Nobel Prize award in 2012. The acceleration of applied research is paving the way for stem cell-based therapeutics to become a common treatment modality in the near future. As human cell manufacturing requires specialised professional skills and knowledge, it is important to promote functional specialisation. These specialisations include donor recruiting, cell manufacturing (where I Peace is the key player), and implementing cell transplant as a medical practice. We believe that creating a systematic industry structure will build awareness and further drive the growth of stem cell-based therapy.

Can you brief Japans licensing key notes to manufacture and process clinical-grade cells in the region?

Japan enacted three laws to promote the use of regenerative medicine as a national policy:

1) The Regenerative Medicine Promotion Act -- representing the country's determination to promote regenerative medicine;

2) The Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act); and

3) The Act on the Safety of Regenerative Medicine (RM Act). The U.S. also has various tracks such as the Regenerative Medicine Advanced Therapy (RMAT) Designation, Breakthrough Therapy designation, and Fast Track designation.

Of significance, the PMD Act enables a fast-track for regulatory approval of regenerative medicalproducts in Japan. In compliance with the RM Act, I Peace was audited by the PMDA and licensed by the Ministry of Health, Labour, and Welfare to manufacture specific cell products.

Because cell product manufacturing regulations are not standardised globally, cell therapy developers are forced to source GMP iPSCs for each market. I Peace however, has overcome this hurdle. We have built in compliance with global GMP regulations, including FDA's cGMP regulations per 21 CFR 210/211 in our operation. As a result, we can provide cells for global use in multiple markets, accelerating both product development and regulatory approval.

Hithaishi C Bhaskar

hithaishi.cb@mmactiv.com

See original here:
"Stem cell-based therapeutics poised to become mainstream option - BSA bureau

To Read More: "Stem cell-based therapeutics poised to become mainstream option – BSA bureau
categoriaIPS Cell Therapy commentoComments Off on "Stem cell-based therapeutics poised to become mainstream option – BSA bureau | dataOctober 5th, 2021
Read All

Asia-Pacific Cell Therapy Market 2021-2028 – Opportunities in the Approval of Kymriah and Yescarta – PRNewswire

By daniellenierenberg

DUBLIN, Aug. 4, 2021 /PRNewswire/ -- The "Asia Pacific Cell Therapy Market Size, Share & Trends Analysis Report by Use-type (Clinical-use, Research-use), by Therapy Type (Autologous, Allogeneic) and Segment Forecasts, 2021-2028" report has been added to ResearchAndMarkets.com's offering.

The Asia Pacific cell therapy market size is expected to reach USD 2.9 billion by 2028. The market is expected to expand at a CAGR of 14.9% from 2021 to 2028.

Rapid advancements in regenerative medicine are anticipated to provide effective solutions for chronic conditions. A substantial number of companies in the growing markets, such as India and South Korea, are striving to capitalize on the untapped opportunities in the market, thereby driving the market.

The growth is greatly benefitted by the fund and regulatory support from government bodies and regulatory agencies. For instance, in August 2020, the government of South Korea passed an Act on the Safety and Support of Advanced Regenerative Medical Treatment and Medicine to establish a regulatory system for patient safety during quality control and clinical trials and to strengthen the regulatory support for regenerative medicine development.

The implementation of the act is expected to enhance clinical studies and approvals of regenerative medicine in South Korea. Furthermore, CAR-T and TCR T-cell therapies have already revolutionized hematologic cancer treatment. With the onset of the COVID-19 pandemic, scientists are deciphering its potential against the novel coronavirus. The concept of using T cells against chronic viral infections, such as HIV and hepatitis B, has already been proposed.

Based on the previous research insights, Singapore-based Duke-NUS medical school's emerging infectious diseases research program demonstrated the utility of these immunotherapies in treating patients with COVID-19 infection.

Thus, an increase in research for use of cell therapies for COVID-19 treatment is expected to drive the market in Asian countries. In April 2021, a team of researchers from Japan used induced pluripotent stem cells (iPS) to find drugs that can effectively inhibit the coronavirus and other RNA viruses.

Key Topics Covered:

Chapter 1 Methodology and Scope

Chapter 2 Executive Summary2.1 Market Snapshot

Chapter 3 Cell Therapy Market Variables, Trends, and Scope3.1 Market Trends and Outlook3.2 Market Segmentation and Scope3.3 Market Dynamics3.3.1 Market driver analysis3.3.1.1 Rise in number of clinical studies for cellular therapies in Asia Pacific3.3.1.2 Expanding regenerative medicine landscape in Asian countries3.3.1.3 Introduction of novel platforms and technologies3.3.2 Market restraint analysis3.3.2.1 Ethical concerns3.3.2.2 Clinical issues pertaining to development & implementation of cell therapy3.3.2.2.1 Manufacturing issues3.3.2.2.2 Genetic instability3.3.2.2.3 Condition of stem cell culture3.3.2.2.4 Stem cell distribution after transplant3.3.2.2.5 Immunological rejection3.3.2.2.6 Challenges associated with allogeneic mode of transplantation3.3.3 Market opportunity analysis3.3.3.1 Approval of Kymriah and Yescarta across various Asian countries3.3.3.2 Developments in CAR T-cell therapy for solid tumors3.3.4 Market challenge analysis3.3.4.1 Operational challenges associated with cell therapy development & usage3.3.4.1.1 Volume of clinical trials for cell and gene therapy vs accessible qualified centers3.3.4.1.2 Complex patient referral pathway3.3.4.1.3 Patient treatment, selection, and evaluation3.3.4.1.4 Availability of staff vs volume of cell therapy treatments3.4 Penetration and Growth Prospect Mapping for Therapy Type, 20203.5 Business Environment Analysis3.5.1 SWOT Analysis; By factor (Political & Legal, Economic and Technological)3.5.2 Porter's Five Forces Analysis3.6 Regulatory Framework3.6.1 China3.6.1.1 Regulatory challenges & risk of selling unapproved cell therapies3.6.2 Japan

Chapter 4 Cell Therapy Market: COVID-19 Impact analysis4.1 Challenge's analysis4.1.1 Manufacturing & supply challenges4.1.2 Troubleshooting the manufacturing & supply challenges associated to COVID-194.2 Opportunities analysis4.2.1 Need for development of new therapies against SARS-CoV-24.2.1.1 Role of T-cell based therapeutics in COVID-19 management4.2.1.2 Role of mesenchymal cell-based therapeutics in COVID-19 management4.2.2 Rise in demand for supply chain management solutions4.3 Challenges in manufacturing cell therapies against COVID-194.4 Clinical Trial Analysis4.5 Key Market Initiatives

Chapter 5 Asia Pacific Cell Therapy CDMOs/CMOs Landscape5.1 Role of Cell Therapy CDMOs5.2 Key Trends Impacting Asia Cell Therapy CDMO Market5.2.1 Regulatory reforms5.2.2 Expansion strategies5.2.3 Rising investments5.3 Manufacturing Volume Analysis5.3.1 Wuxi Biologics5.3.2 Samsung Biologics5.3.3 GenScript5.3.4 Boehringer Ingelheim5.3.5 Seneca Biopharma, Inc.5.3.6 Wuxi AppTech5.4 Competitive Milieu5.4.1 Regional network map for major players

Chapter 6 Asia Pacific Cell Therapy Market: Use Type Business Analysis6.1 Market (Stem & non-stem cells): Use type movement analysis6.2 Clinical Use6.2.1 Market (stem & non-stem cells) for clinical use, 2017 - 2028 (USD Million)6.2.2 Market (stem & non-stem cells) for clinical use, by therapeutic area6.2.2.1 Malignancies6.2.2.1.1 Market (stem & non-stem cells) for malignancies, 2017 - 2028 (USD Million)6.2.2.2 Musculoskeletal disorders6.2.2.3 Autoimmune disorders6.2.2.4 Dermatology6.2.3 Market (stem & non-stem cells) for clinical use, by cell type6.2.3.1 Stem cell therapies6.2.3.1.1 Market, 2017 - 2028 (USD Million)6.2.3.1.2 BM, blood, & umbilical cord-derived stem cells/mesenchymal stem cells6.2.3.1.3 Adipose-derived stem cell therapies6.2.3.1.4 Other stem cell therapies6.2.3.2 Non-stem cell therapies6.3 Research Use

Chapter 7 Asia Pacific Cell Therapy Market: Therapy Type Business Analysis7.1 Market (Stem & Non-stem Cells): Therapy type movement analysis7.2 Allogeneic Therapies7.3 Autologous Therapies

Chapter 8 Asia Pacific Cell Therapy Market: Country Business Analysis8.1 Market (Stem & Non-stem Cells) Share by Country, 2020 & 2028

Chapter 9 Asia Pacific Cell Therapy Market: Competitive Landscape

For more information about this report visit https://www.researchandmarkets.com/r/3hdt1c

Media Contact: Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

http://www.researchandmarkets.com

Original post:
Asia-Pacific Cell Therapy Market 2021-2028 - Opportunities in the Approval of Kymriah and Yescarta - PRNewswire

To Read More: Asia-Pacific Cell Therapy Market 2021-2028 – Opportunities in the Approval of Kymriah and Yescarta – PRNewswire
categoriaIPS Cell Therapy commentoComments Off on Asia-Pacific Cell Therapy Market 2021-2028 – Opportunities in the Approval of Kymriah and Yescarta – PRNewswire | dataAugust 6th, 2021
Read All

Exclusive Report on Stem Cell Therapy in Cancer Market | Analysis and Opportunity Assessment from 2021-2028 |Aelan Cell Technologies, Baylx, Benitec…

By daniellenierenberg

The Stem Cell Therapy in Cancer Market 2021-2028 exploration report by Infinity Business Insights offers an inside and out assessment dependent on Leading Players, Development, Project Economics, Future Growth, Market Estimate, Pricing Analysis, and Revenue.

Rising interests in the structure of a proficient medication dealing with the anchor are projected to give the global Stem Cell Therapy in Cancer market a significant lift in the coming years. Another factor projected to upgrade the global Stem Cell Therapy in Cancer market over the gauge time frame is an expansion in the use of different medication wellbeing programs related to other designing controls.

Get SAMPLE Pages of report @

https://www.infinitybusinessinsights.com/request_sample.php?id=488299

PRIME 30+ players of the Stem Cell Therapy in Cancer Industry:

Aelan Cell Technologies, Baylx, Benitec Biopharma, Bluerock Therapeutics, Calidi Biotherapeutics, Cellular Dynamics International, Center For Ips Cell Research And Application, Century Therapeutics, Khloris Biosciences, Reneuron, & Others.

The pandemic has impacted the worldwide medical services in the Stem Cell Therapy in Cancer market, and nations, for example, Germany and the United States have encountered huge issues. To close the hole in the inventory network, the public authority is putting resources into medical services innovation to satisfy the rising need.

Stem Cell Therapy in Cancer industry -By Application:Hospitals, Specialized Clinics, Academic & Research Institutes, Others,

Stem Cell Therapy in Cancer industry By Product:

Stem Cell And Non-Stem Cell

Contact Us:Amit JainSales Co-OrdinatorInternational: +1 518 300 3575Email: inquiry@infinitybusinessinsights.comWebsite: https://www.infinitybusinessinsights.comFacebook: https://facebook.com/Infinity-Business-Insights-352172809160429LinkedIn: https://www.linkedin.com/company/infinity-business-insights/Twitter: https://twitter.com/IBInsightsLLP

Link:
Exclusive Report on Stem Cell Therapy in Cancer Market | Analysis and Opportunity Assessment from 2021-2028 |Aelan Cell Technologies, Baylx, Benitec...

To Read More: Exclusive Report on Stem Cell Therapy in Cancer Market | Analysis and Opportunity Assessment from 2021-2028 |Aelan Cell Technologies, Baylx, Benitec…
categoriaIPS Cell Therapy commentoComments Off on Exclusive Report on Stem Cell Therapy in Cancer Market | Analysis and Opportunity Assessment from 2021-2028 |Aelan Cell Technologies, Baylx, Benitec… | dataAugust 6th, 2021
Read All

Base Editing as Therapy for Common Inherited Lung and Liver Disease Shows Promise – Clinical OMICs News

By daniellenierenberg

Scientists say that base editing proved itself efficient in correcting a mutation in patient cells with the monogenic disease Alpha-1 antitrypsin deficiency (AATD). The disorder is a common inherited disease that affects the liver and the lungs.

Base editing is different from other forms of editing, including CRISPR, because the base editors do not induce a break in the DNA, which helps prevent double strand breaks, potential off-target editing, and unwanted mutations during cell repair.

Researchers at Boston Medical Center and Boston University used patient-derived liver cells (iHeps) that mimic the biology of liver hepatocytes, the main producers of alpha-1 antitrypsin protein in the body. The base editing technology corrected the Z mutation responsible for AATD and reduced the effects of the disease in the hepatocytes, demonstrating successful base editing in human cells.

The study (Adenine Base Editing Reduces Misfolded Protein Accumulation and Toxicity in Alpha-1 Antitrypsin Deficient Patient iPSC-Hepatocytes), published inMolecular Therapy,can help pave the way for future human trials, according to the research team.

AATD is most commonly caused by the Z mutation, a single base substitution that leads to AAT protein misfolding and associated liver and lung disease. In this study, we apply adenine base editors to correct the Z mutation in patient-induced pluripotent stem cells (iPSCs) and iPSC-derived hepatocytes (iHeps), wrote the investigators.

We demonstrate that correction of the Z mutation in patient iPSCs reduces aberrant AAT accumulation and increases its secretion. Adenine base editing (ABE) of differentiated iHeps decreases ER stress in edited cells as demonstrated by single-cell RNA sequencing. We find ABE to be highly efficient in iPSCs and do not identify off-target genomic mutations by whole genome sequencing.

These results reveal the feasibility and utility of base-editing to correct the Z mutation in AATD patient cells.

This study shows the successful application of base editing technology to correct the mutation responsible for AATD in liver cells derived from patients with this disease, said Andrew Wilson, MD, a pulmonologist at Boston Medical Center and an associate professor of medicine at the Boston University School of Medicine, who served as the studys corresponding author. I am hopeful that these results will create a pathway to use this technology to help patients with AATD and other monogenic diseases.

Base editors created by Beam Therapeutics were applied to induced pluripotent stem cells (iPS cells) from patients with AATD, and then again in hepatocytes that were derived from iPS cells. This was done to study the correction of the Z mutation of the gene responsible for AATD in human cells.

The Z mutation in the SERPINA1 gene is responsible for causing chronic, progressive lung and liver disease in AATD. In patients with AATD, the mutant AAT proteins misfold and form aggregates of protein that build up inside the hepatocytes and cause damage.

For this study, researchers started with mutant (ZZ) iPSCs created from a patient with AATD. After the base editing process was completed, the DNA from the edited cells was sequenced to determine if the SERPINA1 gene had been corrected. Clonal populations of cells with either one (MZ) or both copies (MM) of the corrected gene were expanded and then differentiated over the course of 25 days to generate hepatocytes.

After sequencing the entire genome of the edited cells, there was no evidence of inadvertent mutations in the genome from the base editors, and the misfolding and associated protein buildup was partially corrected in MZ cells and completely in MM normal cells.

The process was repeated using hepatocytes derived from the mutant iPSCs. Two base editors were used in different conditions to test the efficiency of this process. In the best conditions, about 50% of the mutant genes were successfully edited. The cells were then analyzed to see if they still appeared hepatic and if there were fewer signs of the disease in the edited cells, compared to mutant ZZ cells.

Findings showed the base editing did not alter the hepatic program, and the liver cells still expressed hepatic genes and proteins at normal levels. In addition, there was less accumulation of aggregated misfolded Z AAT protein, showing less evidence of disease in the edited cells.

While augmentation therapy has been shown to slow the progression of lung disease in AATD patients, there are currently no treatments available for AATD-associated liver disease. Emerging treatment strategies have focused on the correction of the Z mutation.

Base editing is being evaluated as a treatment modality for a variety of monogenic diseases, according to the scientists. Alpha-1 antitrypsin deficiency is a prime target for base editing, likely to be one of the earlier diseases in which base editors are tried in human studies. Additional disease targets include retinal disease, hereditary tyrosinemia, sickle cell anemia, progeria, cystic fibrosis, and others.

Findings of this study suggest that future research may explore the usefulness of base-editors in editing other quiescent cell populations. Additionally, it has recently been shown that base-editors can edit RNA in addition to DNA in immortalized cell lines and warrants further investigation.

By quiescent, we are referring to differentiated cells (in this case hepatocytes) that are not stem cells or cells that are actively dividing. Basically, [we are talking about] any differentiated cell type, Wilson toldGEN. This is relevant because many of the cell types in the body that you would want to target are already differentiated cells. It is in many cases easier to edit an actively dividing cell, which is why we mention this. There are many examples of a differentiated cell type in the body, such as cardiac cells, lung cells, skin cells, etc., that you might want to target.

One of the major things researchers worry about in the field of gene editing is the possibility of off-target effectsunintended consequences of applying the editing machinery.

The most likely off-target effect, in this case, would be editing of DNA somewhere in the genome other than what we intended to edit, continued Wilson. When we looked by whole genome sequencing, we didnt see evidence of this in iPS cells. However, in addition to editing DNA, it has been reported that base editors can also edit RNA. This could have unintended consequences even if the DNA sequence isnt changed.

We didnt look in this study to see if this occurred, which is why we mentioned itjust to be up front about possible unintended consequences/toxicities that could be present and that we didnt exclude. It isnt something specific to our study or gene of interest but generalizable to the entire field of base editing.

See more here:
Base Editing as Therapy for Common Inherited Lung and Liver Disease Shows Promise - Clinical OMICs News

To Read More: Base Editing as Therapy for Common Inherited Lung and Liver Disease Shows Promise – Clinical OMICs News
categoriaIPS Cell Therapy commentoComments Off on Base Editing as Therapy for Common Inherited Lung and Liver Disease Shows Promise – Clinical OMICs News | dataJuly 22nd, 2021
Read All

MoHAP, EHS reveal immunotherapy for cancer, viral infections at Arab Health 2021 – WAM EN

By daniellenierenberg

ABU DHABI, 22nd June, 2021 (WAM) -- The Ministry of Health and Prevention (MoHAP) and the Emirates Health Services (EHS) recently revealed innovative immunotherapy for cancer and viral infections in cooperation with Japans Kyoto University.

This came during the participation of the ministry and the EHS at the Arab Health 2021 which began in Dubai on 21st June and concludes on 24th June.

The treatment is based on the clinical application of the therapy using T cell preparation after it was discovered that such cells can fight cancer and viral infections. The T cell medicine will be produced using the iPS cell technology.

T Cell makes up a group of lymphocytes present in the blood and plays a major role in cellular immunity. It is possible to produce T cells in large numbers and store them in appropriate conditions to be administered to patients when needed.

Thus, by the success of this project, patients with cancer or viral infection may have great merit in which they can make very easy access to T cell therapy.

Strategic partnerships Dr. Youssef Mohamed Al Serkal, Director-General of the Emirates Health Services, spoke about the commitment of the ministry and the EHS to having strategic partnerships with the most prestigious medical research centres while keeping an eye on the sustainable investment in future healthcare services.

"Although the prevalence of cancer in the UAE is considered lower than in other parts of the world, we work hard to make a qualitative shift in cancer and viral infection healthcare," Al Serkal stated, adding, "This is part of our strategy to provide healthcare services in innovative and sustainable ways and implement the national strategy to reduce cancer mortality rates."

Al Serkal pointed out that the ministry and EHS support the National Cancer Control Programme and prepare a road map to achieve the target indicator. They also analyse the current status of cancer diseases and their diagnostic and therapeutic pathways, support research and studies on the control of cancer diseases and viral infections, and back workshops and educational and training activities. awareness campaigns, and innovative initiatives.

Dr. Kalthum Al Balushi, Director of Hospitals Department, said, "The ground-breaking treatment technology for cancer and viral infections, in cooperation with the Kyoto University, represents a paradigm shift in health services provided by the Ministry and the EHS."

The treatment is based on stimulating immune cells to fight cancer cells using pluripotent stem cells, which is a recent global trend that has begun to open great prospects for improving the quality of life of patients, Al Balushi added.

View post:
MoHAP, EHS reveal immunotherapy for cancer, viral infections at Arab Health 2021 - WAM EN

To Read More: MoHAP, EHS reveal immunotherapy for cancer, viral infections at Arab Health 2021 – WAM EN
categoriaIPS Cell Therapy commentoComments Off on MoHAP, EHS reveal immunotherapy for cancer, viral infections at Arab Health 2021 – WAM EN | dataJune 25th, 2021
Read All

Kiromic Announces Expansion of In-House Cell therapy cGMP Manufacturing Facility and the Appointment of Industry Veteran Ignacio Nez as Chief…

By daniellenierenberg

HOUSTON--(BUSINESS WIRE)-- Kiromic BioPharma, Inc. (Nasdaq: KRBP)

Expansion of in-house cGMP manufacturing facility to provide support to the Company's clinical trials. Therapeutic doses expected to be ready for first in-human dosing in 3Q-2021.

Mr. Ignacio Nez, a 20-year industry veteran in global operations and manufacturing, is joining the Kiromic team to take the company to the next level and to scale up cGMP manufacturing capabilities internally.

Kiromic is an immuno-oncology company using Artificial Intelligence (AI) to identify critical markers in solid tumors to develop Allogeneic CAR-T cell therapy.

Kiromics CAR-T technology addresses critical efficacy and safety issues by developing switches to control T-cell activity reducing cell exhaustion and cytokine release syndrome among others.

-------------

Expansion of in-house cGMP manufacturing facility

In support of the upcoming INDs, Kiromic is expanding its HQ in Houston, TX. To their current cGMP, R&D labs, vivarium and offices, Kiromic is adding an adjacent space where more cGMP clean rooms, QC, QA and regulatory, offices and ultra-cold storage will have place.

This new expansion will add up to a total of approximately 30,000 square feet and will enable supporting Kiromic significant growth as the company approaches the clinical phase.

Appointment of Chief Operating and Manufacturing Officer

Mr. Ignacio Nez MSCHE, MBB has been appointed as Chief Operating Officer and Manufacturing Officer.

Mr. Nez will play a key role in expanding the scale up of Kiromics operations, including manufacturing, taking the company from pre-IND status to the clinical phase and eventually to commercial phase.

Mr. Nez has over 20 years of global experience in corporate functions including manufacturing, research, operational excellence and strategy. He has held senior leadership positions in companies including General Electric, Johnson & Johnson and Novartis. Most recently, he was the Executive Director of Manufacturing at the Gene Therapy Program of the University of Pennsylvania.

Before that, he was the Head of Manufacturing Strategy and Operations Excellence at Novartis, where he was charged with transforming manufacturing operations in support of the ramp up of Kymriah, the first FDA-approved CAR-T cell therapy, which was developed at the University of Pennsylvania.

Mr. Nez holds an MSC in Chemical Engineering from the University of Granada.

CEO of Kiromic, Maurizio Chiriva-Internati, DBSc, PhDs

Kiromic believes it has the key to resolve the current challenges in cell therapy and I believe we will become the reference and lead the industry going forward.

Cell Therapy Manufacturing: Autologous (patient) vs. Allogeneic (healthy donor)

The table below outlines the current cell therapy manufacturing challenges which Kiromic allogeneic cell manufacturing expects to resolve and which Mr. Nez will advance.

CAR-T technology challenges

AutologousCAR-T

KiromicAllogeneic

CAR-T

Safety

CRS

(cytokine release syndrome)

-

+

CRES

(T-cell related encephalopathy syndrome)

-

+

Efficacy

Efficacy

++

++++ (*)

Indication

BloodCancers

SolidTumors

T-cell overstimulation

-

+

T-cell exhaustion

-

+

Tumor immune suppressive microenvironment

-

+

Tumor specific antigens (shedding)

CD19

multipletargets

Manufacturing

Patients variation & manufacturing success

-

+

Lead time(autologous vs. off-the-shelf)

17-30 days

None

Cost of Manufacturing (per patient)

++++

+

Application

Order of treatment application

3rd Line

TBD

Treatment Setting

24 Daysin-patient

24 hoursin-patient (**)

(*) based upon Kiromic's pre-clinical projections, AACR posters (**) as filed in IND to the FDA (May 2021).

COMO of Kiromic, Mr. Ignacio Nez stated:

"I am impressed by Kiromics end-to-end approach to cell therapy as I believe they address almost every known issue in current cell therapies.

Expanded Kiromic in-house manufacturing capabilities are capital efficient and are optimized to deliver the capacity projections, making manufacturing a competitive advantage and not a challenge for the company.

I believe that this technology is meant to change the cell and gene therapy landscape, reshaping the future approach to cancer treatment.

I am humbled to join the team at this critical juncture."

CMO of Kiromic, Scott Dahlbeck, MD, PharmD stated:

Kiromic is pleased to obtain the clinical manufacturing expertise of Mr. Nez, whose expertise and biopharmaceutical background I believe will serve to capitalize on the cellular therapy production capabilities of Kiromic, leading to a new era in immuno-oncology treatments for solid tumors."

CSIO of Kiromic, Mr. Gianluca Rotino stated:

"I believe all of our cell therapy manufacturing is novel and resolves key industry challenges.

It is my opinion, that our manufacturing technology will be very much sought after by pharma companies and cell therapy industry players.

Our cell therapy IPs portfolio is very strong.

This manufacturing expansion and bringing Mr. Nunez to Kiromic are strategically important milestones that makes us ready to face the challenges of the clinical trials and puts us on the path of commercial viability of our novel therapy."

CFO of Kiromic, Mr. Tony Tontat stated:

"Capital efficiency is what we strove to deliver with our investments as we were building out our cGMP facility.

We are happy to receive this additional validation of capital efficiency from an industry veteran like Mr. Nez."

How Our KB-PD1 Live Cell Therapy CAR-T Improves CAR-T Market:

Marketed andtraditional CAR-T

Kiromic KB-PD1

Malignancies(Cancer Type)

Hematologic

Solid Tumors

Live Cell Origin

Autologous

Live Cells from

pre-treatment patients

Allogeneic

Live Cells from

Follow this link:
Kiromic Announces Expansion of In-House Cell therapy cGMP Manufacturing Facility and the Appointment of Industry Veteran Ignacio Nez as Chief...

To Read More: Kiromic Announces Expansion of In-House Cell therapy cGMP Manufacturing Facility and the Appointment of Industry Veteran Ignacio Nez as Chief…
categoriaIPS Cell Therapy commentoComments Off on Kiromic Announces Expansion of In-House Cell therapy cGMP Manufacturing Facility and the Appointment of Industry Veteran Ignacio Nez as Chief… | dataJune 8th, 2021
Read All

Cryopreservation Media helps in Development of a Cell Therapy for Parkinson’s Disease – Microbioz India

By daniellenierenberg

AMSBIO reports upon a publication** that cites how its STEM-CELLBANKER animal-free cryopreservation media has played a role in the development of a cell therapy for Parkinsons Disease that will soon be going into clinical trials.

Parkinsons disease is one of the most common neurodegenerative diseases worldwide. Its main features include motor symptoms such as bradykinesia, rigidity, resting tremor, and postural instability, though non-motor symptoms are often also present. Currently the main therapy for Parkinsons disease consists of augmentation of dopamine levels in the brain via dopamine supplements or agonists or by inhibiting dopamine degradation. Treatment using this methodology is symptomatic but not long-lasting, and unfortunately has no neuroprotective effect. Cell therapy with grafts of human fetal tissue from the ventral mesencephalon have been carried out successfully, with multiple reports of long-term benefits.

A pioneering study from the Centre for Stem Cell Biology at the Memorial Sloan Kettering Cancer Centre (USA) has focused on developing stem cell-derived midbrain dopamine progenitors for the treatment of Parkinsons Disease. This study highlighted, amongst other things, that scientists have been able to demonstrate the efficacy of STEM-CELLBANKER to store, thaw and then recover these manufactured cells for clinical use in patients.

STEM-CELLBANKER is a ready-to-use, chemically defined, animal-free freezing medium manufactured under GMP conditions. It is optimized for embryonic stem (ES) and induced pluripotent stem (iPS) cell storage, as well as being a suitable solution for the cryopreservation of other fragile cell types. Containing only European or US Pharmacopoeia graded ingredients, STEM-CELLBANKER is the optimal choice for storage of cells developed for cell therapy applications. It is also available as a DMSO free formulation. STEM-CELLBANKER significantly increases cell viability while maintaining cell pluripotency, normal karyotype and proliferation ability after freeze-thaw. STEM-CELLBANKER is ready-to-use and requires no special devices, such as a controlled rate freezer, in order to achieve consistently high viabilities following resuscitation from cryopreservation, even over extended long-term storage.

To read the Parkinsons Disease cell therapy paper in full please visithttps://bit.ly/3eYwZ5L. For further information including a video introduction to STEM-CELLBANKER please visithttps://www.amsbio.com/stem-cell-cryopreservation/or contact AMSBIO on +44-1235-828200 / +1-617-945-5033 /info@amsbio.com.

Excerpt from:
Cryopreservation Media helps in Development of a Cell Therapy for Parkinson's Disease - Microbioz India

To Read More: Cryopreservation Media helps in Development of a Cell Therapy for Parkinson’s Disease – Microbioz India
categoriaIPS Cell Therapy commentoComments Off on Cryopreservation Media helps in Development of a Cell Therapy for Parkinson’s Disease – Microbioz India | dataJune 8th, 2021
Read All

Accelerated Biosciences’ Immune-Privileged Human Trophoblast Stem Cells (hTSCs) Offer Breakthrough Opportunities in Cancer-Targeting Therapeutics and…

By daniellenierenberg

CARLSBAD, Calif.--(BUSINESS WIRE)--Accelerated Biosciences, a regenerative medicine innovator, announced today new data that further demonstrates statistically significant cytolysis with induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells programmed from its ethically sourced human trophoblast stem cells (hTSCs). Pluristyx, a Seattle-based firm supporting drug development, regenerative medicine, and cell and gene therapies, further confirmed Accelerated Biosciences hTSC line offers before-unrealized opportunities in cell-specific therapeutics. Along with this recent data on successful iPSC differentiation, Accelerated Biosciences has already demonstrated efficient differentiation of its pluripotent stem cells with remarkable doubling times and growth characteristics to programmed NK, cartilage, bone, fat, neuron, pancreas, liver, and secretome cells.

This new data validates our findings, explains Yuta Lee, President and Founder of Accelerated Biosciences. We know the properties of our trophoblast stem cells have been long-sought by the medical science community because of the potential to speed and amplify the development of life-saving therapeutics; theyre immune privileged, chromosomally stable (not tumorigenic), pathogen free, pluripotent, easy to scale and manufacturer, and of special interest, they are ethically sourced from the chorionic villi (pre-placental tissue) of non-viable and often life-threatening tubal ectopic pregnancies. Mr. Lees father, Professor Jau-Nan Lee, MB, MD, PhD, an obstetrics and gynecologic physician and researcher in Taiwan, first isolated hTSC in 2003. Mr. Lee created Accelerated Biosciences to elevate the visibility of this pluripotent human trophoblast stem cell platform to those engaged in developing allogeneic cell therapeutics and has been instrumental in the filing and prosecution of intellectual property to protect the companys hTSC platform to date holding 34 patents.

Benjamin Fryer, PhD, Co-founder and CEO of Pluristyx, worked closely with Accelerated Biosciences to prepare much of its key hTSC data. Dr. Fryer, a trophoblast expert who was previously a research scientist at Janssen Research & Development of Johnson & Johnson, now serves on Accelerated Biosciences Scientific Advisory Board. Initially I was skeptical these cells were what they said they were. If we hadnt grown and characterized them in our lab, I might have remained skeptical. These are indeed trophoblast stem cells, explained Dr. Fryer. The potential of these cells is enormous. One of the industrys largest challenges is that its almost impossible to scale primary cells. These cells are scalable. With these cells you can make the amount required for millions of patients and theyre sourced compliant to regulatory requirements. Weve made IPS cells (induced pluripotent stem cells) and NK (natural killer) cells from them, which is the next wave of cells for cell therapies. For therapeutic developers, because these cells are not sourced from a person or viable embryo, these cells deliver the trifecta of legal, ethical, and IP advantages.

As the biotechnology industry works toward developing therapies that target only diseased cells without harming healthy cells and tissues, cell-based therapies draw increasing interest, explains industry expert, Martina Molsbergen, CEO of C14 Consulting, who has partnered with Accelerated Biosciences in a business development role. With all the promise that cell therapies hold, the biotechnology industry also remains concerned that the therapeutics are derived in a socially and ethically responsible manner. Accelerated Biosciences has discovered and is now offering what scientists see as the holy grail of stem cell sources.

Prominent biosciences experts have been drawn to Accelerated Biosciences cell breakthrough. Protein chemist and molecular biologist Igor Fisch, PhD, former President and CEO of Selexis, Geneva, Switzerland, recognizes the impact that Accelerated Biosciences hTSCs will have on human health: Not only are these cells politically correct, but they can also differentiate. Because they are sourced from pre-placenta material, theyre immune privileged, which means that are not seen as foreign by the human body. With these cells, we can create a cell bank a single source for a wide range of patients.

Peter Hudson, FTSE, BSc Hons, PhD, Chief Scientist and a senior advisor to Avipep P/L in Melbourne, Australia, and an adjunct professor at the University of Queensland, led a large oncology consortium to complete the first Phase 1 clinical trial of a novel engineered antibody targeting prostate and ovarian cancer. Hudsons interest in Accelerated Biosciences hTSCs has evolved into a role on its Scientific Advisory Board. Trophoblast stem cells are likely to be the next wave of cancer-targeting therapeutics, explains Dr. Hudson. The ability to ethically source trophoblast stem cells and program them to target only diseased, cancerous cells is very powerful technology.

Why are scientists so interested in stem cell-based therapies?

The human body constantly produces specialized cells from its own stem cells (undifferentiated cells) to renew and repair itself. Current therapies harness this power in autologous cell therapies in which the patients own cells are removed, differentiated into disease-fighting cells, and reinserted.

What makes the human trophoblast stem cell so important to medical science?

The human trophoblast stem cell (hTSC) comes from placental tissue and has special properties that make it extremely desirable to therapeutic developers. The hTSC is such an early stem cell that it has much more capacity for growth than a stem cell taken from an adult, for example. This means that one cell can become millions. The hTSC also carries with it the same immune-privilege that a growing embryo has inside its mother: its not seen as foreign although its genetically different than its mother. Unlike other foreign materials, the hTSC is not rejected by the human body, which means that it can be used with many different patients (allogeneic cell therapy). With these benefits, the scientific community holds a high regard for hTSCs, but it also faces socio-ethical concerns about how those stem cells are typically sourced.

Accelerated Biosciences sidesteps hTSC sourcing concerns in a profoundly elegant way. Dr. Jau-Nan Lee, an OB-GYN in Taiwan, found inspiration in what was considered medical waste. When surgical intervention was necessary to remove an ectopic pregnancy that would otherwise risk the womans life, the non-viable embryo and pre-placental tissue lodged in the fallopian tube was removed, sent to pathology, and discarded. Gaining permission from institutional colleagues and sampling the pre-placental tissue, Dr. Lee isolated hTSC that offered all the benefits of hTSC pluripotency, immune privilege, and scalability without pathogens and without ethical compromises.

About Accelerated Biosciences

Founded in 2013, Accelerated Biosciences is a private company focused on regenerative medicine and built around the hTSC discoveries of obstetrics and gynecology physician and researcher, Professor Jau-Nan Lee, MB, MD, PhD. Accelerated Biosciences holds a large and robust patent portfolio and an encumbrance-free intellectual property (IP) estate. Accelerated Biosciences mission is to leverage its renewable, immune-privileged human cell source to fuel breakthrough cell therapies that effectively target the most challenging diseases of the human body. For more information about Accelerated Biosciences, visit acceleratedbio.com or email mmolsbergen@c14consultinggroup.com.

Read more here:
Accelerated Biosciences' Immune-Privileged Human Trophoblast Stem Cells (hTSCs) Offer Breakthrough Opportunities in Cancer-Targeting Therapeutics and...

To Read More: Accelerated Biosciences’ Immune-Privileged Human Trophoblast Stem Cells (hTSCs) Offer Breakthrough Opportunities in Cancer-Targeting Therapeutics and…
categoriaIPS Cell Therapy commentoComments Off on Accelerated Biosciences’ Immune-Privileged Human Trophoblast Stem Cells (hTSCs) Offer Breakthrough Opportunities in Cancer-Targeting Therapeutics and… | dataMay 15th, 2021
Read All

Factor Bioscience to Deliver Six Digital Presentations at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting – PRNewswire

By daniellenierenberg

Factor reveals advances in mRNA, circleRNA, gene editing, cell reprogramming, and iPS cell-derived NK-cell technologies.

Digital presentations will be made available on the ASGCT website on May 11, 2021. For more information on the upcoming American Society of Genetic & Cell Therapy (ASGCT) Annual Meeting, visit https://annualmeeting.asgct.org/

About Factor BioscienceFounded in 2011, Factor Bioscience develops technologies for engineering cells to advance the study and treatment of disease. Factor collaborates with academic and industrial partners to develop therapeutic products based on its mRNA, gene editing, cell reprogramming, and nucleic-acid delivery technologies. Factor Bioscience is privately held and is headquartered in Cambridge, Massachusetts. For more information, visit http://www.factorbio.com.

Media Contact:

Allen Mireles[emailprotected]

Related Linkshttp://www.factorbio.comhttps://annualmeeting.asgct.org/

SOURCE Factor Bioscience Inc.

http://www.factorbio.com

Follow this link:
Factor Bioscience to Deliver Six Digital Presentations at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting - PRNewswire

To Read More: Factor Bioscience to Deliver Six Digital Presentations at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting – PRNewswire
categoriaIPS Cell Therapy commentoComments Off on Factor Bioscience to Deliver Six Digital Presentations at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting – PRNewswire | dataMay 15th, 2021
Read All

St. Jude’s $11.5B, six-year plan aims to improve global outcomes for children with cancer and catastrophic diseases – The Cancer Letter

By daniellenierenberg

Small dreams have no power to move hearts, and in a new six-year strategic plan, St. Jude Childrens Research Hospital is thinking very big.

What would it take to drastically increase cure rates for childhood cancer worldwide?

St. Judes answer: $11.5 billion and an additional 1,400 jobs.

To get a rough sense of scale, work it out with a pencil:

Spread over six yearsat $1.916 billion each yearits just under a third of the NCIs annual spend, fourfold this years projected revenues of the American Cancer Society, and more than seventyfold the budget of the World Health Organizations International Agency for Research on Cancer.

Its a broad and ambitious plan that will allow the institution to grow at an almost 8% compound annual growth rate, James Downing, president and CEO of St. Jude, said to The Cancer Letter.

At a global level, we also want to see identifiable increases in cure rates. We are watching those very carefully. Our goal is to move toward cure rates of 60% for diseases like acute lymphoblastic leukemia, Hodgkins lymphoma and Wilms tumor, Downing said. As we look at a global population, survival rates hover around 20%, and wed like to see those go up year by year.

A lot of our efforts are based on implementation science, looking at what works and what doesnt work. Workforce, drug distribution and true advancements in cure rates are what were seeking over the next six years.

The plan, rolled out on April 27, calls for an acceleration of research and treatment globallynot just for pediatric cancer, but also other illnesses, including blood disorders, neurological diseases, and infectious diseases.

Not surprisingly, this amount represents the largest investment the Memphis, Tenn. hospital has made in its nearly 60-year history. The previous strategic plan, the largest expansion in the institutions history, resulted in $7 billion in investments (The Cancer Letter, May 19, 2017).

The multi-phase expansion plan is funded almost entirely by steadily increasing donor contributions generated by ALSAC, the fundraising and awareness organization for St. Jude.

It is an ambitious plan. But were going to have lots of new personnel, new investments, new technology and new partnerships. We have formal partnerships with many U.N. associate agencies and organizations around the world.

Within the past six years, St. Jude has advanced fundamental, clinical, and translational research, Downing said.

Two years ago, we began strategically looking at the most pressing issues in the field of pediatric cancer, Downing said. As we developed the strategic plan over those two years, there were many ideas we critically assessed, and we often said, Its not really best for St. Jude to pursue that.

In the end, we aligned on goals that collectively bring the prospect of remarkable benefits to the field of childhood cancer, and to children with cancer everywhere.

On campus, St. Jude accepted nearly 20% more new cancer patients; increased faculty by 30% and staff by 23%; and embarked on several large-scale construction projects.

The new strategic plan focuses on five areas: fundamental science, childhood cancer, pediatric catastrophic diseases, global impact, and workforce and workplace culture.

Were coming out of a six-year strategic plan in which we increased our number of cancer patients by 20%, with 30% new faculty, 23% more staff, many large-scale construction projects, said Charles Roberts, executive vice president of St. Jude and director of the hospitals Comprehensive Cancer Center. And were now going into a new strategic plan that is 60% larger than our prior plan.

Under the plan, St. Jude will hire nearly 70 new faculty members, plus supporting laboratory staff, to work in basic, translational, and clinical research across 22 departments.

These investigators will have the freedom to pursue the type of conceptually driven research that leads to tomorrows clinical advances.

As we launch a strategic plan, weve identified the most exciting opportunities and challenges at that point in time, Roberts said to The Cancer Letter. However, we fully realize that we dont know whats coming next. New discoveries will be made, and new opportunities will emerge. Via the blue-sky process, weve set aside substantial funds every year to invest in the pursuit of emerging opportunities suggested by faculty and staff.

Part of what brought me here from Boston was the last strategic plan, and its so exciting to be a part of this. But just looking at the numbers, 1,400 new positions, average salary of $90,000. Six hundred and forty of those positions are in research, 266 are in clinical, 100 are in global pediatric medicine, and 394 in support.

Those are the kinds of numbers that you need to make these things real, and I think its exciting for St. Jude and for the field of cancer research, as we bring in all of these new folks.

During the next six years, St. Jude will invest more than $250 million to expand technology and resources available to scientists and clinicians in their search to understand why pediatric catastrophic diseases arise, spread and resist treatments. These investments will include:

St. Jude will invest $3.7 billion during the next six years to expand cancer-focused research and related clinical care. These efforts will center on raising survival rates for the highest-risk cancers and for children with relapsed diseases, while simultaneously improving quality of life for pediatric cancer survivors. The investments will include:

In the U.S., more than 80% of children diagnosed with cancer will be cured. In contrast, 80% of children with cancer live in limited-resource countries, where a mere 20% survive their disease. To address this, St. Jude will more than triple its investment in its international efforts coordinated through St. Jude Global and the St. Jude Global Alliance during the next six years.

This represents an investment of more than $470 million. Global initiatives include:

Under the plan, St. Jude will expand research and treatment programs to advance cures for childhood catastrophic diseases. The $1.1 billion, six-year investment includes work in nonmalignant hematological diseases, such as sickle cell disease; a new laboratory-based research program in infectious diseases that affect children worldwide; and a new research and clinical program to better understand and treat pediatric neurological diseases.

The plan outlines several strategies to encourage teamwork, and internal and external collaboration. These will include:

It is estimated that 87% of funds to sustain and grow St. Jude over the next six years will come from public donations.

Patients at St. Jude do not receive a bill for treatment, travel, housing or fooda model established by ALSAC and St. Jude founder Danny Thomas, who believed in equal access to medical care and driving research advances.

There are an incredible number of donors across the United States who support St. Jude, Downing said. This carries a great responsibility for us to seek the maximum possible impact to improve outcomes for childhood cancer.

Downing and Roberts spoke with Matthew Ong, associate editor of The Cancer Letter.

Matthew Ong: Congratulations on the official launch of St. Judes second six-year strategic plan. Could you briefly walk us through whats in it?

James Downing: It is an exciting time for St. Jude Childrens Research Hospital. Were finishing our prior six-year strategic plan, which started in Fiscal Year 2016. That $7 billion investment in the organization spanned fundamental science, clinical and translational research, clinical operations, and our global efforts. During the course of the plan, we increased faculty by 30% and staff by 23% and accelerated progress against pediatric catastrophic diseases.

About two years ago, we started discussing the next strategic plan. We looked critically at what we had accomplished under the previous plan, the expertise we had assembled, and the major problems in the field of pediatric catastrophic diseases, including cancer, infectious diseases, nonmalignant hematologic diseases and pediatric neurologic diseases. During that period, we involved more than 200 individuals across the institution to develop the new strategic plan.

This plan, at its core, focuses on accelerating progress against pediatric catastrophic diseases on a global scale. It outlines a $11.5 billion investment during the next six years, which includes the addition of 1,400 jobs and $1.9 billion in new capital investments, construction and renovations. Its a broad and ambitious plan that will allow the institution to grow at an almost 8% compound annual growth rate.

The plan has 11 goals, divided among five major areas: fundamental science, pediatric cancer, other childhood catastrophic diseases, global impact, and a focus on people and place. In each of these areas, were recruiting new individuals, investing in new technology, and expanding collaborations across campus, across the United States, and globally.

Ill start with fundamental science. In our last strategic plan, we invested heavily in increasing basic science programs on campus by expanding faculty numbers, technology and institutional data infrastructurein the belief that expanding fundamental science leads to new knowledge that helps advance cures. This is investigator-initiated science, often not related to diseases, but rather to the fundamental questions of biology.

In this new plan, were again investing heavily in expanding fundamental science at St. Jude. Weve committed more than $1 billion to fundamental science. This includes increasing laboratory-based faculty by more than 33% during the next six years, and more than $250 million dedicated to investments in technology.

Our goal is to make sure every dollar is spent wisely and effectively in pursuit of our missionto advance cures and means of prevention for pediatric catastrophic diseases through research and treatment.

The $250 million will fund multiple shared resources, department-based technology centers and new centers of excellence. Some of the faculty are being recruited to the centers of excellence, including those in data-driven discovery, innate immunity and inflammation, leukemia and advanced microscopy. These individuals will also have homes in academic departments.

On the technology front, were investing in shared resources. Well bring online some new ones, as well as some (Center for Modeling Pediatric Diseases and the Center for High-Content Screening) created at the end of the last strategic plan. The newest is focused on spatial transcriptomics. It will allow scientists across campus to look at the expression of genes in tissue context and at the single-cell level.

A new effort in structural biology is to create a $20 million Cryo-Electron Tomography Center. This is the next level of cryo-electron microscopy, which allows the identification of the structure of molecules or molecular machines within the context of cells. Its a developing technology that will feed other investments weve made in structural biology, such as the installation of one of the largest magnets in the world in our NMR facility, our Cryo-Electron Microscopy Center and single-cell analysis capabilities. The plan brings those tools to bear on defining normal biology and disease states.

Another effort is a Center of Excellence in Advanced Microscopy. Over the last six years, weve become one of the leading centers in the application of advanced microscopy to fundamental biology. This has been led by investigators in our Developmental Neurobiology, Cell and Molecular Biology, and Immunology departments.

Were positioned to build the next generation of microscopes to explore biology in ways never dreamed. With new faculty recruitments and collaborations with commercial companies and other institutions, we seek to develop the next generation of microscopes, and apply that to normal biology and to pediatric catastrophic diseases.

Another area were investing in heavily is data science. Over the last six years, and even before that, we expanded data sciences across campus. This initially started with the Pediatric Cancer Genome Project in 2010. Since then, we recruited many data scientists, and coalesced them into our Computational Biology, Biostatistics, and Epidemiology and Cancer Control departments, and into shared resources that provide bioinformatics support.

But over the last several years, weve seen the explosion of data, from structural biology to microscopy.

As we look to the future and the capabilities weve amassed, were poised to significantly increase our investment in data science and become a leading institution in the application of data science to biologic discovery. This is a $40 million investment with 30 full-time employees.

We have a task force led by faculty members to develop the roadmap for how were going to move forward. As data is accumulated and we look across those disparate data types, we can gain knowledge through true data scienceexploring that data and advancing our understanding of biology.

The last area in fundamental research is our graduate school. During the last strategic plan, we developed the St. Jude Graduate School of Biomedical Sciences, which offers a PhD and two masters programs.

Were going to expand that over the coming six years by increasing the number of students in the Biomedical Sciences PhD, the Master of Science in Global Child Health and the Master of Science in Clinical Investigations programs. We will also create a new masters program in data science. That will bring a new population of students to campus, which will further enhance our scientific enterprise.

Pediatric cancer is our next area of focus. This has always been our institutions major focus. This area encompasses $3.7 billion of the operating dollars we will spend over the next six years. Although weve invested heavily in this effort in the past, were going to expand it significantly.

Were going to focus on pediatric cancers where the least progress has been madecancers that are incurable and relapsed diseaseand gain insights into how we can change the outlook for those cancers.

The first area of investment is new faculty10 laboratory-based individuals who will expand our research efforts in understanding the biology of cancer. Some of those faculty will go into the Center of Excellence in Leukemia, but others will focus on solid tumors, brain tumors, or on biologic aspects that cut across cancer types.

Our second area for expansion will focus on assessing new therapeutic approaches for the highest-risk cancers. We need to access and evaluate more new therapies in a rigorous manner to identify those which should be moved forward into frontline clinical trials. Pediatric cancer encompasses many different types of cancer.

To run clinical trials, you need a sufficient number of patients to be able to answer questions in a reasonable time frame. We need a way to identify the best new agents to move into clinical trials.

Our investment in preclinical testing will help us set up that infrastructure. Much of it was established in the last strategic plan, but it must be expanded so that we have the best pediatric cancer models and can assess single and combination therapies to see which are worth moving forward into clinical trials.

On the clinical trial front, we want to expand our infrastructure to run those clinical trialsnot only on our campus, but in collaborations across the United States and around the globe. To make progress in some of these high-risk pediatric cancers, we need many patients. For many of the high-risk cancers, there are not a sufficient number of patients in the United States to conduct the trials. We, therefore, need to set up global collaborative networks that can address these high-risk cancers.

So, were investing in our ability to access drugs through commercial sources, to rigorously assess these in preclinical models and to establish the global infrastructure to run these clinical trials with an associated translational science infrastructure second to none.

Our third emphasis under the cancer focus is cancer immunotherapy. We began our work in cancer immunotherapy decades ago. We developed the chimeric antigen receptor, or CAR, against CD-19. That is the basis for the FDA-approved therapy that is being used right now on a variety of different fronts. Over the last several years, weve also invested heavily in expanding our cancer immunotherapy efforts, primarily focused on CAR-modified T cells.

As part of this new strategic plan, we are creating a new program, the Translational Immunology and Immunotherapy Initiative. It will facilitate cross-departmental efforts focused on cancer immunotherapy and will explore the fundamental biology of chimeric antigen receptor approaches to cancer immunotherapy.

What makes an ideal antigen that can be attacked by a chimeric antigen receptor? How does one manipulate CAR T cells so that they undergo exhaustion and stop killing the tumor? How do we change that? And what are the features of the microenvironment that decrease the killing potency of CAR T cells? These will require significant investments, including additional faculty.

Another emphasis will be looking at long-term toxicities of the therapies we use to treat children with cancer. As we cure more and more pediatric cancers, we must continually look at the toxicities from therapy and figure out how to reduce those without sacrificing the ability to be cured. Part of that is precision medicine, and so we are continuing to invest in our genomic and pharmacogenomic efforts and our proton therapy center.

Part of reducing toxicities comes from learning from long-term survivors. So, we will continue to invest in St. Jude LIFE, our long-term, follow-up study. We will expand that to some of the newer pediatric cancer therapies, including immunotherapy and targeted agents. We will assess long-term complications from these therapeutic approaches and try to define which patients will be susceptible to these toxicities.

MO: I have to mention the obvious: $11.5 billion is quite the budget. Your new strategic plan is work that, one could argue, might be on par or exceeds the coordination and budget required to realize multiple projects, say, at the World Health Organization or even at some U.S. federal agencies. What did it take for you and your team at St. Jude to get to this point?

JD: There are an incredible number of donors across the United States who support St. Jude. Our goal is to make sure every dollar is spent wisely and effectively in pursuit of our missionto advance cures and means of prevention for pediatric catastrophic diseases through research and treatment. This carries a great responsibility for us to seek the maximum possible impact to improve outcomes for childhood cancer.

We have the ideal team at St. Jude to execute this. Our leadership meets multiple times each week. Two years ago, we began strategically looking at the most pressing issues in the field of pediatric cancer. We discussed which areas represented the greatest opportunities for St. Jude to contribute. We talked to many experts inside and outside of the institutionaround the globeand made hard decisions as we went forward.

Strategic planning is deeply engrained at St. Jude as a rigorous process that is part of our scientific culture. We knew it was going to take two years to develop this plan. We dont hire consultants; we do it all ourselves. Faculty across the institution participated in the development of priorities and goals for this strategic plan via structured meetings.

As we developed the strategic plan over those two years, there were many ideas we critically assessed, and we often said, Its not really best for St. Jude to pursue that. In the end, we aligned on goals that collectively bring the prospect of remarkable benefits to the field of childhood cancer, and to children with cancer everywhere.

Every child who comes on this campus is part of our mission. We provide them with the best care possible. We do that in the context of research studies, so that were learning from every single patient. That means were not only helping children today; were also advancing cures for children tomorrow.

Weve rolled out the new strategic plan across campus during the last month, and the excitement is palpable. Our commitment continues long after the strategic plans launch.

We have routine strategic planning retreats, where we assess the goals for the year, evaluate progress against the prior years goals, perform talent assessments and proactively seek out emerging opportunities. Every employee on campus will develop yearly goals that cascade down from the goals of this plan.

As we develop this roadmap, we know there are going to be new ideas. Charlie can tell you about a process incorporated into the strategic plan that allows us to not only move forward on this roadmap, but also add initiatives as new ideas emerge.

Charles Roberts: Its a process we began with the last strategic plan, called our blue-sky process. As we launch a strategic plan, weve identified the most exciting opportunities and challenges at that point in time.

However, we fully realize that we dont know whats coming next. New discoveries will be made, and new opportunities will emerge. Via the blue-sky process, weve set aside substantial funds every year to invest in the pursuit of emerging opportunities suggested by faculty and staff.

Ideas that have emerged from the blue-sky process have been phenomenal. Our engagement with World Health Organization (WHO)a collaboration to raise childhood cancer survival rates internationallyis one example.

The Center for Modeling Pediatric Diseases is another example. This center makes iPS cells that come from patients so that we can investigate mechanisms that underlie cancer predisposition.

In another blue-sky project, were looking at DNA methylation to characterize pediatric solid tumors with the goal of identifying new therapeutic opportunities. Some of our immunotherapy initiatives also came out of the blue-sky process. Were looking forward to growing our blue-sky endeavors as we go forward.

Were coming out of a six-year strategic plan in which we increased our number of cancer patients by 20%, with 30% new faculty, 23% more staff, many large-scale construction projects. And were now going into a new strategic plan that is 60% larger than our prior plan.

The other central part of our strategic planning process focuses on the importance of collaboration. We have systematically incorporated a focus upon collaboration into our entire strategic planning and execution process. Our strategic planning efforts began by bringing together the intellectual resources of faculty and staff at St. Jude. This yielded projects that have interactions between many investigators on campus.

We recognize, however, that were still a relatively small institution, and theres a lot of expertise outside. We asked: How can we engage top scientists to tackle problems related to cancer and other catastrophic illnesses of childhood?

In pursuit of this, during our last strategic plan, we created the St. Jude Research Collaboratives, in which we fund investigators from multiple institutions who collaborate with investigators at St. Jude.

Initially, we were planning to fund two or three Collaboratives. However, they were remarkably successful, and top scientists eagerly joined.

Consequently, weve grown the program to five St. Jude Research Collaboratives already. These teams are each funded at an average of $8 million over 5 years, so each investigator is getting R01-level funding, or a little bit better. This has been a phenomenal success.

In the new strategic plan, were going to grow the program to a steady state of 11 funded collaboratives, representing close to a $90 million investment. So far, three of the Collaboratives are directly focused on childhood cancer. A fourth is a basic science-focused project relevant to childhood cancer. Were excited about the growth of this collaboration-focused program.

Lastly, Id like to address global collaboration. If you look across the globe, in low- and middle-income countries, the cure rates for childhood cancer are less than 20%.

This is a problem we know we can solve. Weve proven in the United States we can drive the cure rate to 80%. How can we help the rest of the world?

Because of the resources brought to us by our donors, we are able to think about these things, and so were now collaborating around the globe to drive cure rates forward for childhood cancer worldwide.

JD: As an example of new ideas and how rapidly we can act on them, Id like to tell you about a new blue-sky proposal that came up at the end of the last strategic plan. This idea was precipitated at a faculty retreat. One of our senior investigators was presenting, and during a coffee break, someone said, Well, what if you did this? That emerged into a blue-sky proposal, Seeing the Invisible in Protein Kinases. This was work from Dr. Babis Kalodimos, our Structural Biology department chair. He had a Science paper that came out several months ago, where he used the high-field NMR spectroscopy to look at the structure of the ABL kinase. He was able to identify transient conformational states that help to explain how resistant mutants work.

This gave us new insights into transient states that exist in molecules that can only be seen under high-field NMR, not with other structural biology approaches.

Based on that, we started thinking, Well, what if you did this on all kinases? What if you just did it against tyrosine kinases, serine kinases, receptor tyrosine kinases? What new rules would emerge from this? What would it tell us about families of kinases? What would it tell us about mechanisms of inhibition to kinase inhibitors? What might it tell us about new approaches to developing drugs against protein tyrosine kinases?

And since kinases are a major focus for targeted therapy, there was great excitement about pursuing these studies. Dr. Kalodimos developed the proposal and brought it forward; however, it was clear that this effort would be beyond the scope of our blue-sky process.

Blue-sky initiatives are usually somewhere in the $12 million range, and this was north of $30 million. Yet, in the end after thorough internal and external reviews, the project will move forward as part of the new strategic plan..

This is an approach that will give us fundamental knowledge and can have a profound impact on our understanding of a major class of targets for next-generation therapy.

MO: If I recall accurately, St. Jude has a network of partnerships with a few dozen countries worldwide. Does this plan call for an expansion of efforts within each of those countries? And how many of them?

JD: When I took over in 2014, we had what we called the International Outreach Program, which was 24 programs in 17 countries. During the programs 25-year history, we had made great progress. We were making significant impact and changing the outlook for children with cancer in those 17 countries. But we were affecting only about 3% of children with cancer across the globe, and the International Outreach Program was not scalable.

So, at the beginning of the last strategic plan, we recruited Dr. Carlos Rodriguez-Galindo. He developed a vision that after assessing, we decided to move forward on. This new effort encompasses the Department of Pediatric Global Medicine, St. Jude Global and the St. Jude Global Alliance.

These are all integrated. We developed a model that we think is scalable around the world, and we think this model ultimately can affect children with cancer everywhere.

The idea is that first we must train a workforce to treat children with cancer around the globe. We cant train the workforce ourselves, but we can train the trainers, who will then train the workforce.

More:
St. Jude's $11.5B, six-year plan aims to improve global outcomes for children with cancer and catastrophic diseases - The Cancer Letter

To Read More: St. Jude’s $11.5B, six-year plan aims to improve global outcomes for children with cancer and catastrophic diseases – The Cancer Letter
categoriaIPS Cell Therapy commentoComments Off on St. Jude’s $11.5B, six-year plan aims to improve global outcomes for children with cancer and catastrophic diseases – The Cancer Letter | dataMay 15th, 2021
Read All

Synthego Launches Eclipse Platform to Accelerate Research and Development of Next-generation Medicines – The Scientist

By daniellenierenberg

Synthego, the genome engineering company, today announced the launch of Eclipse, a new high-throughput cell engineering platform designed to accelerate drug discovery and validation by providing highly predictable CRISPR-engineered cells at scale through the integration of engineering, bioinformatics, and proprietary science. The launch of this unique CRISPR-based platform is driving the companys growing impact in biopharma R&D, reinforcing Synthegos position as the genome engineering leader.

CRISPR-engineered cells have a wide range of applications in research and development across disease areas, including in neuroscience and oncology. Synthego created the Eclipse Platform to enhance disease modeling, drug target identification and validation, and accelerate cell therapy manufacturing.

"By industrializing cell engineering, Synthegos Eclipse Platform will enable economies of scale, turning a historically complex process into one that is flexible, reliable, and affordable, said Bill Skarnes, Ph.D., professor and director of Cellular Engineering at The Jackson Laboratory and Synthego advisory board member. Offering CRISPR edits at scale, similar to what Synthego did with sgRNA reagents, puts researchers on the cusp of being able to study thousands of genes, and examine hundreds of variants of those genes. This will allow scientists to more faithfully model the complexity of a human disease, which could lead to the development of therapeutic drugs or next-generation gene therapies for many serious diseases.

To ensure the success of any type of edit, Eclipse uses machine learning to apply experience from several hundred thousand genome edits across hundreds of cell types. With this machine learning, combined with automation, the new platform can reduce costs and increase the scalability of engineered cell production. The Eclipse Platform is modular in design, allowing for fast deployment of upgrades or add-ons. It is engineered to use a cell-type agnostic process and immediately benefit researchers working with induced pluripotent stem (iPS) cells and immortalized cell lines.

We are living in a new era of life sciences innovation one that has added to DNA sequencing and being able to read out of biology, now being able to write into and engineer biology. We created our Eclipse Platform at the convergence of science and technology to make genome editing more precise, scalable, and accessible, said Paul Dabrowski, CEO and co-founder of Synthego. We are excited to expand our impact on advancing the life sciences innovation with the launch of this unique CRISPR-based platform.

Go here to read the rest:
Synthego Launches Eclipse Platform to Accelerate Research and Development of Next-generation Medicines - The Scientist

To Read More: Synthego Launches Eclipse Platform to Accelerate Research and Development of Next-generation Medicines – The Scientist
categoriaIPS Cell Therapy commentoComments Off on Synthego Launches Eclipse Platform to Accelerate Research and Development of Next-generation Medicines – The Scientist | dataApril 19th, 2021
Read All

The Google Play video app will leave Roku, Vizio, LG and Samsung’s TV platforms – Yahoo Canada Finance

By daniellenierenberg

Google is discontinuing the Google Play Movies and TV app for Samsung, LG and Vizio smart TVs, as well as Roku devices. Come June 15th, 2021, you wont be able to access the software on those platforms anymore. Instead, youll need to go through YouTube to watch any content youve bought in the past. Any Google Play credits associated with your account will still be there, allowing you to buy new movies and TV shows. However, your Watchlist wont transfer over, and support for family sharing is more limited.

Google shared the news last month, but it went mostly unnoticed until after websites like Liliputing and 9to5Google published stories on the shutdown earlier today following an email the company sent to users. To be clear, Play Movies and TV itself isnt joining the Google graveyard on June 15th. Google plans to eventually merge the app with its new Google TV software, but that's an ongoing process with the former still available to download on Android and iOS.

Read the original post:
The Google Play video app will leave Roku, Vizio, LG and Samsung's TV platforms - Yahoo Canada Finance

To Read More: The Google Play video app will leave Roku, Vizio, LG and Samsung’s TV platforms – Yahoo Canada Finance
categoriaIPS Cell Therapy commentoComments Off on The Google Play video app will leave Roku, Vizio, LG and Samsung’s TV platforms – Yahoo Canada Finance | dataApril 19th, 2021
Read All

New Controversy for Stem Cell Therapy That Repairs Spinal Cords – The Great Courses Daily News

By daniellenierenberg

By Jonny Lupsha, Current Events WriterAn alternative to using human embryonic stem cells is to use pluripotent stem cells, which refers to the ability of a stem cell, such as skin cells from an adult, to give rise to other differentiated cell types. Photo By Yurchanka Siarhei / Shutterstock

Patients who have received treatment from their own stem cells to repair their spinal cords are at the center of controversy after the stem cell therapy was fast-tracked in Japan in 2018. Despite 13 patients showing considerable recovery in response to the treatment, the means to this end have suggested improper shortcuts taken in the last several years.

It isnt the first time that stem cell research has been in the spotlight for ethical reasons. One controversial method of obtaining stem cells is to take them from human embryos, which has been argued about for decades. However, alternatives to embryo use are coming to pass.

In his video series Biochemistry and Molecular Biology: How Life Works, Dr. Kevin Ahern, Professor of Biochemistry and Biophysics at Oregon State University, said much about stem cells and the science that surrounds them.

There are two things that are special about stem cells, Dr. Ahern said. One is that they are capable of dividing indefinitelythat is, as long as the organism is alive. The other is that they are undifferentiatedtheyre like a child who hasnt yet chosen whether to be an astronaut, ballerina, surgeon, or an artist.

Dr. Ahern said that when stem cells divide, they can either differentiate and become a specialized cell or they can go back into the stock of stem cells. In an embryo, at the earliest stages of development, the fertilized egg divides to produce a certain number of unspecialized cells called embryonic stem cells. They become specialized by receiving certain signals, so scientists can learn what these signals are and send them to unspecialized cells to make them develop as they wish. This could mean making them become cells to repair nerve damage, heart muscles, and more.

However, some see this as tampering with nature and/or stealing cells from the embryo. Regardless of our opinions one way or the other, these ethical concerns have been raised, prompting scientists to find alternatives.

How else can stem cells be obtained, if not from embryos?

One solution is the production of what are called induced pluripotent stem cells, or iPS cells, Dr. Ahern said. Pluripotent refers to the ability of a stem cell to give rise to other differentiated cell types. To do this and yet avoid working with cells from a human embryo, scientists begin with differentiated somatic cells [like] cells from the skin of an adult, for example.

Once theyve isolated the differentiated somatic cells, scientists reverse engineer them into a state in which they can become any number of differentiated cells or tissues. Dr. Ahern said that iPS cells have been used to create beating heart cells, motor neurons, light-sensing photoreceptor cells, insulin-producing pancreatic cells, and more.

In 2017, Japanese researchers reported that monkeys with Parkinsons showed great improvement after treatment with dopamine-producing neurons derived from iPS cells, Dr. Ahern said. In 2018, clinical trials with humans were begun using iPS cells to treat Parkinsons, heart disease, and macular degeneration.

For now, stem cell therapy remains no stranger to controversyor results. The debate raging around them will likely continue in one way or another for some time.

Edited by Angela Shoemaker, The Great Courses Daily

Originally posted here:
New Controversy for Stem Cell Therapy That Repairs Spinal Cords - The Great Courses Daily News

To Read More: New Controversy for Stem Cell Therapy That Repairs Spinal Cords – The Great Courses Daily News
categoriaIPS Cell Therapy commentoComments Off on New Controversy for Stem Cell Therapy That Repairs Spinal Cords – The Great Courses Daily News | dataMarch 8th, 2021
Read All

Page 3«..2345..1020..»


Copyright :: 2024