LIFESAVING After being on the Be the Match registry for eight months, Lacey Jones donated stem cells to a 75-year-old woman battling myeloid leukemia.

A Kokomo teacher has spent part of her summer possibly saving the life of a 75-year-old woman.

Late last month, Lacey Jones, a veterinary careers instructor at the Kokomo Area Career Center, traveled to the Hoxworth Blood Center at the University of Cincinnati to donate stem cells to a woman she was genetically matched with who was battling myeloid leukemia. Now, all Jones hopes is that her stem cells were enough.

I really want nothing more than to hear that she is in remission. That was the emotional part of the process. Once it was all over, I just went to my hotel room, and I could not help but to just kind of cry and cry and cry and pray and hope because you want nothing more than for your cells to work for the patient, Jones said.

But the opportunity to help someone was a chance that some dont ever get. Jones registered as a donor through Be the Match, which operates the national bone marrow registry, late last year after the story of her friends daughter, who was diagnosed with infant leukemia, inspired her to want to help someone.

According to Be the Match, only one of 430 people who register as a donor is selected as a match, and some of those who are selected wait years before theyre matched. For Jones, she became a genetic match for someone in just eight months.

At the end of May, she received a call from Be the Match, letting her know that there was a woman who had been diagnosed with myeloid leukemia, and Jones was a secondary match for her. Jones was told that there was someone who was the primary match who matched just a little better, but in the chance that that donor fell through, Jones would be at the plate.

I just kind of waited around, didnt really think anything of it, and then they called me at the beginning of June. She explained that the original person who matched ended up not being who they really needed, and of course with HIPPA and all that they cant really tell you any of that information as to why, Jones said.

As far as the patient, all Jones was told was that it was a 75-year-old woman who was battling myeloid leukemia somewhere in the world. Jones was asked if shed be available to donate during certain dates, but at that point, there were no details as to where she would be donating or exactly when. What Jones did know, though, was that she would do it.

The process then became a whirlwind of scheduling, logistics, and injections. She went to Indianapolis for lab work to ensure she was healthy enough to donate. Then, for a week leading up to her donation, she was required to take injections of a drug called filgrastim to increase the number of white blood cells in her bloodstream so they could be collected more easily.

Theyre actual injections that are given to people who have cancer to increase the white blood cell count, but theyre given to donors because it increases your bone marrow production. Then what happens is your body naturally expels the extra bone marrow into the bloodstream, she said.

Jones was a bit hesitant because shed never given herself injections before, and she was warned of the side effects that could occur. The most common side effect of filgrastim, she said, was soreness due to the overproduction of bone marrow.

They explained some of the side effects of the filgrastim, and that makes you feel a little intimidated. But because of my passion and my empathy for the patient and hearing about there not being donors and just knowing that I could potentially help save her life, it overruled any type of fear I had, she said.

At the end of June, Jones traveled to Hoxworth Blood Center at the University of Cincinnati to begin the donation.

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There are two donation methods, either marrow or peripheral blood stem cells. The marrow donation is a surgical procedure done under anesthesia. Doctors use needles to retrieve liquid marrow from both sides of the back of a patients pelvic bone. The hospital stay is usually from early morning to late afternoon, according to Be the Match, while some donors are kept overnight for observation.

The peripheral stem cell donation, on the other hand, is a non-surgical procedure that takes place at a blood center or outpatient hospital. Blood is removed through a needle in one arm and passed through a machine that collects only the blood-forming cells and returns the blood through a needle in the donors other arm.

As soon as Jones got to the blood center, nurses took a blood sample to see where her white blood cell count was. A normal count, she said, was between four and 10. Hers was at 42. Because the filgrastim injections were so effective for Jones, she was able to do the peripheral stem cell method.

So began a five-hour process of Jones sitting very still while a machine filtered out blood-forming cells from her left arm and put the blood back in her right arm. The nurses took her blood pressure every 15 minutes to ensure she wasnt having any kind of reaction, and the staff knew down to the minute when her donation would be complete, she said, and had the transfer staff ready.

At the end of the donation, Jones said it was like a movie when the person came in to take her stem cells that would be delivered to the patient.

They actually had somebody come up with the cooler because they flew my sample to the patient. Its almost like a movie. You watch someone come through the big steel door with the cooler and watch them package your sample, she said.

And while she didnt know where the sample was going, she was told the recipient was nowhere close to where they were.

When the process was over, Jones was thankful. She said the nurses told her it was a textbook donation, and the only side effect Jones experienced from the injections was mild soreness.

Three months after the donation, the recipient will have the option to find out who her donor was and to contact Jones if she chooses.

Jones said shed love to one day hear from the recipient.

I want nothing more than to one day get that phone call that says, OK, the person you donated to wants to get in contact with you. I dont know what Ill do. Ill probably cry again, she said.

Jones will remain on the Be the Match registry, and in the event she ever receives a call that shes a match again, she will be ready to go, she said.

To join the bone marrow donor registry, visit join.bethematch.org. The process requires a cheek swab, which can be done with a kit thats mailed to potential donors. Afterward, the person will be added to the registry and have the chance to get matched.

Be the Match encourages those who are contacted to donate to go forward with the donation as theyre the patients best genetic match from the entire registry.

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Donating a chance at life: Kokomo teacher donates stem cells to 75-year-old woman through Be the Match - Kokomo Perspective

58% relapse free survival at 1 year post-transplant79% overall survival at 1 year post-transplant

BOSTON, July 21, 2021 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53, today announced positive results from its Phase 2 trial evaluating eprenetapopt with azacitidine for post-transplant maintenance therapy in patients with TP53 mutant MDS and AML.

In 33 patients enrolled in the trial, the relapse free survival (RFS) at 1 year post-transplant was 58% and the median RFS was 12.1 months. The overall survival (OS) at 1 year post-transplant was 79%, with a median OS of 19.3 months. Prior clinical trials evaluating post-transplant outcomes in TP53 mutant MDS and AML patients have reported a 1-year post-transplant RFS of ~30% and a median OS of ~5-8 months. In addition, the post- transplant regimen of eprenetapopt and azacitidine was well tolerated among patients in the clinical trial. The Company plans to discuss the data from this Phase 2 clinical trial with the U.S. Food and Drug Agency (FDA) in the second half of 2021 and expects to present data at a future scientific or medical conference.

The post-transplant RFS and OS data with eprenetapopt and azacitidine maintenance therapy in these very difficult-to-treat TP53 mutant MDS and AML patients are incredibly exciting, said trial principal investigator Asmita Mishra, M.D., of the H. Lee Moffitt Cancer Center and Research Institute. Although transplant is currently the only potentially curative treatment for patients with TP53 mutant MDS and AML, the risk of relapse with current standard of care remains unacceptably high and the median OS post-transplant is very limited at 8 months or less. Post-transplant maintenance therapy with eprenetapopt and azacitidine could, if approved, represent a new treatment paradigm that meaningfully improves outcomes for these patients with limited treatment options.

About Aprea Therapeutics, Inc.

Aprea Therapeutics, Inc. is a biopharmaceutical company headquartered in Boston, Massachusetts with research facilities in Stockholm, Sweden, focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53. The Companys lead product candidate is eprenetapopt (APR-246), a small molecule in clinical development for hematologic malignancies and solid tumors. Eprenetapopt has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA for myelodysplastic syndromes (MDS), Orphan Drug and Fast Track designations from the FDA for acute myeloid leukemia (AML), and Orphan Drug designation from the European Commission for MDS and AML. APR-548, a next generation small molecule reactivator of mutant p53, is being developed for oral administration. For more information, please visit the company website at http://www.aprea.com.

The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.

About p53, eprenetapopt and APR-548

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

Eprenetapopt (APR-246) is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein by restoring wild-type p53 conformation and function thereby inducing programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with eprenetapopt in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase 1/2 clinical program with eprenetapopt has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.

A pivotal Phase 3 clinical trial of eprenetapopt and azacitidine for frontline treatment of TP53 mutant MDS has been completed and failed to meet the primary statistical endpoint of complete remission. A Phase 1/2 clinical trial of eprenetapopt with venetoclax and azacitidine for the frontline treatment of TP53 mutant AML met the primary efficacy endpoint of complete remission. Additional clinical trials in hematologic malignancies and solid tumors are ongoing. Eprenetapopt has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA for MDS, Orphan Drug and Fast Track designations from the FDA for AML, and Orphan Drug designation from the European Medicines Agency for MDS and AML.

APR-548 is a next-generation small molecule p53 reactivator. APR-548 has demonstrated high oral bioavailability, enhanced potency relative to eprenetapopt in TP53 mutant cancer cell lines and has demonstrated in vivo tumor growth inhibition following oral dosing of tumor-bearing mice.

About MDS

Myelodysplastic syndromes (MDS) represent a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of MDS and AML patients and are associated with poor overall prognosis. There are no currently approved therapies specifically for TP53 mutant MDS or AML patients.

About AML

AML is the most common form of adult leukemia, with the highest incidence in patients aged 60 years and older. AML is characterized by proliferation of abnormal immature white blood cells that impairs production of normal blood cells. AML can develop de novo or may arise secondary to progression of other hematologic disorders or from chemotherapy or radiation treatment for a different, prior malignancy; secondary AML carries a worse prognosis than de novo AML. Mutations in TP53, which are associated with poor overall prognosis, occur in approximately 20% of patients with newly diagnosed AML, more than 30% of patients with therapy-related AML and approximately 70-80% of patients with complex karyotype.

Forward-Looking Statement

Certain information contained in this press release includes forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as future, predicts, believes, potential, continue, anticipates, estimates, expects, plans, intends, targeting, confidence, may, could, might, likely, will, should or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or other studies, risks associated with the coronavirus pandemic and the other risks set forth in our filings with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Source: Aprea Therapeutics, Inc.

Corporate Contacts:

Scott M. Coiante Sr. Vice President and Chief Financial Officer 617-463-9385

Gregory A. Korbel Sr. Vice President and Chief Business Officer 617-463-9385

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Aprea Therapeutics Announces Positive Results from Phase 2 Trial of Eprenetapopt + Azacitidine ... - The Bakersfield Californian

Dr. Bill Cimikoski, Medical Director of Utah Stem Cellsjoined Surae on The Daily Dish to discuss the BodyTite and Facetite procedures. He tells Surae that these procedures are excellent for getting rid of unwanted fat, while at the same time shrink wrapping the skin so that any loose skin is simultaneously tightened at the same time.

For some individuals, there may only be minimal (or none at all) fat to extract and it might be only necessary to tighten the skin. Depending on the area Utah Stem Cells are treating, they often see that in some individuals, there isnt really any fat to speak of and their patients are just looking for skin tightening and this is an excellent way to achieve that goal!

Unfortunately, on the other hand, some patients do have a large amount of fat in certain areas and then this device is also accompanied by liposuction. This is where they can suck the fat in addition to tightening the loose skin at the same time.This procedure is called Radio Frequency assisted Liposuction. At Utah Stem Cells they also offer High Definition Radio Frequency assisted liposuction to sculpt abs.

They offer many different treatments for different areas of the body, including the following:

All procedures are in-office and with only small holes or needle punctures, which heal completely without scarring. There is no need for general anesthesia and all are completed with lidocaine fluid although they do offer nitrous oxide, ketamine, and other methods to keep people comfortable and less anxious.

As a special gift, anyone who calls in after viewing The Daily Dish today will be entitled to $200 off any procedure.

To find out more about how Dr. Bill Cimikoski and Utah Stem Cells can help you, visit their website or you can give them a call at Phone number: (801) 999-4860

This article contains sponsored content.

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Learn how to remove unwanted fat with procedures beyond liposuction - ABC 4

SAN DIEGO--(BUSINESS WIRE)--Stemson Therapeutics announced today the closing of a DCVC Bio-led $15 million Series A financing to advance development of Stemsons proprietary therapeutic solution to cure hair loss. Genoa Ventures, AbbVie Ventures and other investors join in supporting Stemsons efforts to restore human hair growth with a novel cell regeneration technology using the patients own cells to generate new hair follicles.

In addition, Kiersten Stead, Ph.D., Co-Managing Partner at DCVC Bio and Jenny Rooke, Ph.D., Managing Director at Genoa Ventures will join Stemsons Executive Chairman Matt Posard and Chief Executive Officer and co-founder Geoff Hamilton on the board of directors. Dr. Stead invests in early-stage companies that build novel deep tech businesses in the life sciences. Stead received a Ph.D. in Molecular Biology & Genetics and an MBA in finance from the University of Alberta. Dr. Rooke is founder and Managing Director at Genoa Ventures where she specializes in early-stage companies innovating at the convergence of technology and biology. Rooke received a Ph.D. in Genetics from Yale University and a degree in physics from the Georgia Institute of Technology.

We are excited and honored to welcome DCVC Bio and a fantastic syndicate of investors to the Stemson team. The Series A funding will help us optimize our solution for human skin structure and environment so we can go into our first human clinical trial with high confidence for a positive outcome. We have the technical and biological building blocks to successfully address hair loss that overcomes failures of past therapies, said Hamilton. The addition of key venture capital investors DCVC Bio, Genoa Ventures and AbbVie Ventures broadens and strengthens our investor base. DCVC Bio and Genoa Ventures are successful early-stage development investors, and I am pleased to welcome Dr. Stead and Dr. Rooke, our newest board members, to the team. In addition, the AbbVie Venture investment comes on the heels of an initial seed investment from Allergan Aesthetics in 2020, and the continued industry interest in our technology is encouraging.

Globally, hundreds of millions of men and women suffer from various forms of hair loss. Though there are many possible causes of hair loss, including chemotherapy, autoimmune disease, scarring, and genetics, all can result in a loss of self-esteem and cause depression, anxiety and other mental health disruption for those affected. The hair restoration market is expected to exceed $13.6 billion by 2028, and no solution today is capable of generating an unlimited new supply of healthy follicles for patients in need.

Almost 30 years have passed since the last FDA-approved hair loss treatment, yet millions still suffer the physical and mental impact of losing their hair each year, stated Dr. Stead. Stemsons novel stem cell engineering platform has the potential to cure hair loss once and for all, treating not only the physical symptoms of this complex problem, but the mental burden as well.

"The team at Genoa is impressed with Stemsons vision to blend biology and technology and apply it beyond traditional biotech," added Dr. Rooke. "By combining exciting advancements in iPSCs with novel technologies in materials and data sciences, Stemson exemplifies the kind of chimeric teams Genoa seeks to support on their journey to become a category-defining company."

The Series A financing brings the total funding raised to date to $22.5 million and allows Stemson to further the next stage of research and development of its cell engineering platform, where is it being combined with bioengineered material and robotic delivery as a novel solution for natural hair replacement. Currently, Stemsons research and development efforts are focused on developing an optimized solution for human skin structure environment in larger animal models. Stemsons Induced Pluripotent Stem Cell (iPSC) based technology is capable of producing the cell types required to initiate hair follicle growth and have been successfully tested in small animal models.

About Cell Regeneration Technology

Human Induced Pluripotent Stem Cells (iPSC) have the unique capability to replicate indefinitely and give rise to all cell types of the human body, including the cell types required for repair. iPSC-based technology is capable of producing the cell types required to initiate hair follicle growth. As a new therapeutic platform, iPSCs represent an emerging area of regenerative cell therapy. Stemson is one of a growing number of companies at the forefront in developing iPSC-based treatments.

About DCVC Bio

For over twenty years, DCVC and its principals have backed brilliant entrepreneurs applying Deep Tech, from the earliest stage and beyond, to pragmatically and cost-effectively tackle previously unsolvable problems in nearly every industry. DCVC Bio specializes in supporting life sciences platform companies at the intersections of engineering and therapeutics, industrial biotechnology and agriculture. For more information, please visit https://www.dcvc.com/companies.html#dcvc-bio

About Genoa Ventures

Genoa Ventures invests in early-stage companies working at the convergence of biology & technology to accelerate the pace of innovation, transform industries, and solve some of the most fundamental challenges to life. Genoa, identifies opportunities early and focuses its investments and expertise to empower the next great category-defining companies. The Genoa team has a unique chimeric blend of experience from scientific research and discovery to executive management in the life sciences and technologies sectors. The team applies this diverse experience to provide expert guidance to its companies and stellar returns to its investors.

About AbbVie Ventures

AbbVie Ventures is the corporate venture capital group of AbbVie. We are a strategic investor, investing exclusively in novel, potentially transformational science aligned with AbbVie's core R&D interests. We measure success primarily by the extent to which our investments foster innovation with potential to transform the lives of patients that AbbVie serves. AbbVie Ventures enables its portfolio companies with both funding as well as access to AbbVie's internal network of experts across all phases of drug development, from drug discovery through commercialization. For more information, please visit http://www.abbvie.com/ventures

About Stemson Therapeutics

Stemson Therapeutics is a pre-clinical stage cell therapy company founded in 2018 with a mission to cure hair loss by leveraging the regenerative power of Induced Pluripotent Stem Cells. Based on the breakthrough innovation by Stemson Therapeutics co-founder, Dr. Alexey Terskikh, Stemson uses iPSC to regenerate the critical cells required to grow hair and which are damaged or depleted in patients suffering from hair loss. The iPSC-derived cells are used to grow de novo hair follicles, offering a new supply of hair to treat people suffering from various forms of Alopecia. Today, there are no available treatments capable of growing new hair follicles. Stemsons world class team of scientists, advisors and collaborators are passionate about delivering a scientifically based, clinically tested cure for hair loss to the millions of hair loss sufferers who seek help for their hair loss condition. Stemson Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.stemson.com.

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Stemson Therapeutics Secures $15M Series A Funding to Cure Hair Loss - Business Wire

Blood cancers are not like other cancers. Unlike a cancer that affects one region of the body, such as lung cancer afflicting the lungs, blood cancers affect the entirety of the body because blood flows throughout it. Blood cancers do not form a lump or tumor in a specific organ, potentially making blood cancers more difficult to detect.

Blood contains various components. Red blood cells, white blood cells, plasma, and platelets all combine to make blood. Blood cancers, which include lymphoma, leukemia and myeloma, affect different components of the blood and interfere in different ways with the normal function of blood in the body.

Lymphoma affects the lymphatic system, which includes white blood cells called lymphocytes. These cells help protect the body against infection, advises the health site OnHealth. Leukemia originates inside of the bone marrow. Production of an overabundance of white blood cells may impede the marrows ability to make sufficient red blood cells and plasma, states the Leukemia & Lymphoma Society. Myeloma affects plasma cells, a type of white blood cell that fights off infection. When they become cancerous, the affected white blood cells can manufacture an abnormal protein that may damage organs and bodily systems.

Individuals affected with lymphoma, leukemia or myeloma may not feel a tumor, but they can look out for other symptoms. These include:

Frequent infections;

Coughing or chest pain;

Fever or chills;

Ongoing weakness or fatigue;

Shortness of breath;

Night sweats; and/or

Itchy skin or rash.

Even though blood cancers differ from other cancers in the way they present and what parts of the body they affect, they often are initially treated in the same way. SurvivorNet, a cancer survivor resource, says chemotherapy and radiation can target these cancers. Stem cell transplant, also known as bone marrow transplant, is a much more common treatment for blood cancers. Stem cells may be extracted from the patient or received from a donor.

Those who suspect the presence of blood cancers should consult with a doctor who can order blood tests to form a diagnosis.

We are making critical coverage of the coronavirus available for free. Please consider subscribing so we can continue to bring you the latest news and information on this developing story.

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What sets blood cancers apart from other cancers? | Lifestyles | washtimesherald.com - Washington Times Herald

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.

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

Q: Im considering having my own stem cells injected into me to improve physical and mental problems that I am having post-COVID-19 infection. What do you think?

James D., Huntington, N.Y.

A: Theres been a lot of talk about using what are called autologous stem cells (your own) to fight off COVID-19 long-haul symptoms, as well as to treat everything from torn ligaments to Alzheimers disease. None is approved by the Food and Drug Administration. The only stem-cell-based products that are FDA-approved come from blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood and theyre for treating disorders involving production of blood (the hematopoietic system). A list is at fda.gov; search for Approved Cellular and Gene Therapy Products.

In fact, stem cell/regenerative medicine treatment scams are so prevalent that this spring the FDA finally told manufacturers and marketers that they had to comply with regulations on human cell and tissue products. Unfortunately, a June report from Pew Trust found compliance by the companies and enforcement from the FDA to be anemic.

What the report did find was that more than 700 clinics in the U.S. offer unapproved stem-cell and regenerative medicine interventions for conditions such as Alzheimers, muscular dystrophy, autism, spinal cord injuries and, most recently, COVID-19. They also found post-injection infection happens frequently and is likely because of sloppily manufactured products and failure to properly screen for diseases such as HIV and hepatitis B and C.

If youre considering stem-cell treatment, the FDA urges you to ask the clinic for the following info before getting it even if the stem cells are your own:

Proof the FDA has reviewed and approved the treatment. Have your primary care doc confirm the information.

If the clinic is claiming it has an FDA-issued Investigational New Drug application number, ask for it and ask to review the FDA communication acknowledging the IND.

Stem-cell treatment has great potential, but when used for unapproved therapies outside a clinical trial, its risky (and expensive). To search for a trial, go to clinicaltrials.gov.

Q: My doctor says my high blood pressure puts me at increased risk for dementia. I think hes just trying to get me on one more med. Is there really a connection?

Lacie R., Sacramento, Calif.

A: Dementia means that you have cognition problems that cause trouble with memory, thought and everyday tasks. That could result from mini- or regular strokes, and we know that high blood pressure increases your stroke risk. In fact, one Harvard study found that high blood pressure increases a mans risk of stroke by 220 percent; another found that each 10 mmHg rise in systolic pressure (the top number) boosts your risk of ischemic stroke by 28 percent and of hemorrhagic stroke by 38 percent.

Even if your high blood pressure doesnt trigger a stroke, it can lead to impaired cognition and dementia. The 2018 SPRINT-MIND trial found that intensive control of high blood pressure (getting the top number below 120) lowered the risk of mild cognitive impairment by 19 percent compared with standard blood pressure control. Now, a new study in the journal Hypertension indicates that certain antihypertensive medications ACE inhibitors and ARBs (and angiotensin II receptor blockers) can cross the blood-brain barrier and lower dementia risk. Tracking almost 13,000 people for three years, the researchers found that folks taking those meds showed less memory loss than folks taking other sorts of antihypertensive medications.

You dont indicate how high your blood pressure is, but if it is only slightly elevated you may be able to bring it down through changing your diet, losing weight if you need to and exercising for 30 to 60 minutes five days a week. If it is above 125 (top number) or above 85 (bottom number), a combo of those self-care techniques and medication may be the safest choice. But either way, bringing your blood pressure to around 115/75 will protect your brain, as well as your heart, kidneys and eyes.

Contact Drs. Oz and Roizen at sharecare.com.

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Stemming the tide of stem-cell treatment scams - Houston Chronicle

Wei Wu and Xiao-Ming Xu (Credit: IU School of Medicine)

Researchers at Indiana University School of Medicine (Indianapolis, USA) have announced the successful reprogramming of a glial cell type in the central nervous system into new neurons in order to promote recovery after spinal cord injuryrevealing an untapped potential to leverage the cell for regenerative medicine.

This is the first time that scientists have reported modifying a NG2 gliaa type of supporting cell in the central nervous systeminto functional neurons after spinal cord injury, saidWei Wu, research associate in neurological surgery at IU School of Medicine and co-first author of the paper, which was published in the Cell Stem Cell journal.

Wu andXiao-Ming Xu, the Mari Hulman George professor of Neuroscience Research at IU School of Medicine, worked on the study with a team of scientists from the University of Texas Southwestern Medical Center.

Spinal cord injuries affect hundreds of thousands of people in the United States, with thousands more diagnosed each year. Neurons in the spinal cord dont regenerate after injury, which typically causes a person to experience permanent physical and neurological ailments.

Unfortunately, effective treatments for significant recovery remain to be developed, Xu said. We hope that this new discovery will be translated to a clinically relevant repair strategy that benefits those who suffer from a spinal cord injury.

When the spinal cord is injured, glial cells, of which there are three typesastrocyte, ependymal and NG2respond to form glial scar tissue.

Wu added: Only NG2 glial cells were found to exhibit neurogenic potential in the spinal cord following injury in adult mice, but they failed to generate mature neurons. Interestingly, by elevating the critical transcription factor SOX2, the glia-to-neuron conversion is successfully achieved and accompanied with a reduced glial scar formation and increased functional recovery following spinal cord injury.

The researchers reprogrammed the NG2 cells from the mouse model using elevated levels of SOX2a transcription factor found inside the cell thats essential for neurogenesisto neurons. This conversion has two purposes, Xu said: to generate neurons to replace those lost due to a spinal cord injury and reduce the size of the glial scars in the lesion area of the damaged tissue.

This discovery, serves as an important target in the future for potential therapeutic treatments of spinal cord injury, adds Wu, who goes on to note that such a collaboration will be continued between the two laboratories to address neuronal remodelling and functional recovery after successful conversion of glial cells into functional neurons in future.

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IU School of Medicine researchers discover new potential for functional recovery after spinal cord injury - Spinal News International

Researchers at the Chinese Academy of Sciences and University of Science and Technology of China have devised a novel bioprinting-based method of curing previously untreatable spinal cord injuries.

Using a custom bio-ink, the Chinese team have managed to 3D bioprint neural stem cell-loaded tissues capable of carrying instructions via impulses from the brain, much like those seen in living organisms. Once implanted into disabled rats, the scaffolds have shown the ability to restore movement in paralyzed limbs, and the scientists now believe their approach could find human applications in future.

There is no known effective cure for spinal cord injury, Zhijun Zhang, a nanobiomedical engineer at the Chinese Academy of Sciences told the Scientist. The 3D bioprinting strategy weve developed, may represent a general and versatile strategy for rapid and precise engineering of the central nervous system (CNS), and other neuronal tissues for regenerative medicine.

The SCI injury conundrum

A Spinal Cord Injury or SCI is a blanket term used to describe any damage caused to the bundle of cells and nerves that send signals to and from the brain along the human spinal cord. While the damage itself can be caused either by direct injury, or from bruising to the surrounding vertebrae, the result is often the same: a partial or complete loss of sensory and locomotor function below the affected area.

While theres no current known cure for SCI, a number of promising cell-based therapies are now being developed, with the regeneration of functional neurons seen as central to their future success. In effect, such approaches involve re-establishing links between neurons throughout the injured area in order to restore nerve functionality, but repairing damaged cells continues to be problematic.

Where neural stem cells have previously been implanted into SCI sites, theyve also shown poor viability and uncontrolled differentiation, leading to low therapeutic efficacy. More recent efforts have seen scientists bioprint cell-loaded scaffolds, capable of creating a suitable microenvironment in which neurons can flourish, yet this has raised further issues around printability and initiating cellular interaction.

To get around these problems, the Chinese researchers have now developed a novel bio-ink that gels together at body temperature to prevent neurons from differentiating into cells that dont produce electrical impulses, and can be 3D bioprinted into scaffolds that not only mimic the white matter appearance of the spine, but encourage cell-to-cell interactions.

A paralysis cure in-action

To begin with, Zhang and his team formulated their bio-ink from natural chitosan sugars, as well as a mixture of hyaluronic acids and matrigel, before combining them with rat neural stem cells. The scientists then used a BioScaffolder 3D bioprinter to deposit the resulting concoction into cell-laden scaffolds, which were later stored in culture plates for further testing.

Prior to their implantation, the teams different samples were incubated for three, five and seven days respectively, during which they proliferated and formed connections. Interestingly though, the researchers found that the higher the concentration of hyaluronic acid, the lower levels of interaction they observed, showing that their bio-ink can be tweaked to achieve desired tissue characteristics.

When injected into paraplegic lab rats, the scaffolds exhibited a cell viability of 95% while promoting neuron regeneration to the point that they enabled the rats to regain control over their hind legs. Over a 12-week observation period, the treated animals also showed a revived ability to move their hips, knees and ankles without support, and kick pressure sensors with markedly enhanced muscle strength.

As a result, the scientists have concluded that their approach offers a versatile and powerful platform for building precisely-controlled complex neural tissues with potential human applications, although they concede that more precise regulation of cell differentiation will be needed to achieve this, in addition to further testing on more clinically-relevant injury models.

Overall, this study clearly demonstrated for the first time the feasibility of the 3D bioprinted neural stem cell-laden scaffolds for SCI repair in-vivo, concluded the team in their paper, which, we expect, may move toward clinical applications in the neural tissue engineering, such as SCI and other regenerative medicine fields in the near future.

3D bioprinting in CNS treatments

Thanks to constant advances in flexible electronics and 3D bioprinting technologies, its now becoming increasingly possible to produce neural implants, with the potential to treat complex CNS injuries. Last year, a project started at TU Dresden led to the creation of 3D printed neural implants, capable of linking the human brain to computers as a means of treating neurological conditions such as paralysis.

In a similar study, engineering firm Renishaw has worked with pharmaceuticals expert Herantis Pharma to assess the performance of its 3D printed neuroinfuse drug delivery device. Designed to deliver intermittent infusions into the parenchyma, an organs functional tissue, the platform could be used as a future treatment for Parkinsons disease.

With regards to treating spinal injuries specifically, researchers at the University of California San Diego have also managed to repair spinal cord injuries in rats. By implanting 3D printed two-millimeter-wide grafts into test subjects, the team have been able to facilitate neural stem cell growth, restore nerve connections and ultimately help recover limb functionality in rodent test subjects.

The researchers findings are detailed in their paper titled 3D bioprinted neural tissue constructs for spinal cord injury repair. The study was co-authored by Xiaoyun Liu, Mingming Hao, Zhongjin Chen, Ting Zhang, Jie Huang, Jianwu Dai and Zhijun Zhang.

The nominations for the 2021 3D Printing Industry Awards are now open. Who do you think should make the shortlists for this years show? Have your say now.

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Featured image shows the researchers 3D bioprinted scaffolds after 7 and 21 days culturing. Images via the Biomaterials journal.

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Introducing the 3D bioprinted neural tissues with the potential to 'cure' human paralysis - 3D Printing Industry

In the last few years, many researchers have discovered that mesenchymal stem cells (MSCs) hold the key to treating many serious diseases such as diabetes, Parkinsons disease, and multiple sclerosis. According to the study, Prevalence of Parkinsons disease (PD) across North America, published in July 2018 in the journal Nature, the number of people suffering from PD is expected to reach 930,000 in 2020 and 1,238,000 in 2030. Thus, high prevalence of such diseases is also expected to aid in growth of the mesenchymal stem cells market.

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While no one yet knows exactly how the cells work, scientists are excited about the potential benefits of using MSCs as treatment modalities. In particular, the discovery that stem cells can differentiate into other cell types has implications for the field of regenerative medicine. The potential of MSCs to provide treatments for age-related diseases is exciting. Thus, increasing geriatric population is also expected to aid in growth of the mesenchymal stem cells market.

While stem cells from adults hold the most promise for use in treating human illnesses, the discovery that adult stem cells can be directed to treat specific diseases has provided doctors with a new approach to the treatment of patients with life-threatening diseases, which in turn is expected to aid in growth of the mesenchymal stem cells market. Mesenchymal stem cells are found in the bone marrow in rich supply. Because the cells are continually being used to make blood, tissue, and organs, they are not only rich in blood, they are also rich in antigens. This allows adult stem cells to directly apply their healing properties to a host of diseases.

Adult MSCs have the potential to replace diseased or otherwise damaged adult stem cells in a variety of tissues throughout the body, including muscle, bones, and organs. Various researches have revealed exciting potential in using these cells to treat a range of debilitating diseases. For example, since MSCs can be directed to the myeloid tissues of the bone marrow, they can help to repair and regenerate tissue and organs that are injured or became infected. These studies are currently underway and have the potential to provide a major breakthrough in the treatment of many serious diseases, boosting growth of the mesenchymal stem cells market.

MSCs are also being tested to directly apply to a patients spinal cord to promote regrowth of bones and other skeletal tissues. This is done through the introduction of specialized cells into the spinal cord. Since the specialized cells that are made in the laboratory from MSCs can be directed to a number of myeloid tissues, they can provide a direct means of repairing and regenerating spinal cord injury, spinal stenosis, cervical spondylosis, spinal arthritis, etc. The long term effects of mesenchymal stem cells transplantation on the spinal cord are not yet known but the studies so far are very promising and the technology could very soon be available for clinical trials.

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Major Key Players Are: Pluristem Therapeutics, LonzaThermo, Fisher, ATCC, Bio-Techne, MilliporeSigma, Genlantis, Celprogen, Cell Applications, PromoCell GmbH, Cyagen Biosciences, Human Longevity Inc., Axol Bioscience, Cytori Therapeutics, Eutilex Co.Ltd., ID Pharma Co. Ltd., BrainStrom Cell Therapeutics, Cytori Therapeutics Inc., Neovii Biotech, Angel Biotechnology, California Stem Cell Inc., Stemcelltechnologies Inc., and Celgene Corporation Inc.

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Mesenchymal Stem Cells Market Witnesses Upward Trend with High Prevalence of Parkinson's Disease The Manomet Current - The Manomet Current

The clinical evidence included high concentrations of C-X-C motif chemokine ligand 10 (CXCL10) and C-C motif chemokine ligand 2 (CCL2) in the cerebrospinal fluid (CSF) and serum samples.

This interim report supports the feasibility of generating HER2-specific CAR T cells for repeated dosing regimens and suggests that their repeated intra-CNS delivery might be well tolerated and activate a localized immune response in pediatric and young adult patients, Nicholas Alexander Vitanza, MD, an assistant professor at the Ben Towne Center for Childhood Cancer Research, and a staff member of the Cancer and Blood Disorders Center, Brain Tumor Program, Apheresis, at Seattle Childrens, and coauthors, wrote in the study publication.

Although the integration of CAR T-cell therapy has provided a novel therapeutic modality to manage multiple hematologic malignancies, the utility of CAR T cells is not fully understood for pediatric patients with CNS tumors.

HER2 offers a valid target for CAR T-cell therapy in CNS tumors because it is widely expressed on a significant proportion of biologically diverse CNS tumors such as ependymoma, glioblastoma, and medulloblastoma, as well as CNS cancer stem cells. Moreover, HER2 is not expressed on normal CNS tissue.

Monoclonal antibodies, such as trastuzumab (Herceptin), are beneficial for patients with some HER2-expressing cancers but have limited activity in CNS tumors that require a therapy that crosses the blood-brain barrier. CNS tumors also harbor less HER2 expression compared with malignancies like breast cancer.

As such, directly administering HER2-directed therapy to the tumor site could be a lucrative strategy for patients with CNS tumors.

Preclinical data demonstrated that spacer length was correlated with improved activity of HER2-specific CAR T cells. Based on this, the single-institution BrainChild-01 trial used a medium-length spacer HER2CAR to evaluate repeated locoregional delivery of HER2-specific CAR T cells for pediatric patients with recurrent or refractory CNS tumors.

Following CAR T-cell manufacturing, patients were treated in the outpatient setting for up to 6 courses. Course 1 consisted of 3 weeks of a 1 x 107 dose of CAR T cells (DL1), followed by clinical evaluation in week 4. Course 2 consisted of 1 week of DL1 treatment, 2 weeks of a 2.5 x 107 dose of CAR T cells (DL2), followed by clinical and radiographic evaluation in week 4. Courses 3 through 6 retained the same dosing schedule at the highest tolerated dosing levels, which included 2 additional tiers: 5 x 107 [DL3] and 10 x 107 [DL4].

The BrainChild-01 HER2CAR T-cell product was manufactured under a process designed to yield balanced numbers of CD4+ and CD8+ lentivirally transduced T cells exhibiting limited terminal differentiation with enrichment for the CAR+ population of cells mid-culture, Vitanza and coauthors wrote.

The initial 3 patients were required to be from 15 to 26 years old. This age group is more capable of self-reporting neurologic changes compared with a younger patient population, so they were specifically used for the initial evaluation.

The first eligible 3 patients underwent apheresis and had CAR T-cell products that were in-line with release criteria. As such, the patients were assigned to the appropriate treatment arms: repeated locoregional CNS infusion into the CNS tumor or tumor cavity (arm A; n = 1) vs repeated locoregional CNS infusion into the ventricular system (arm B; n = 2).

All patients had undergone at least 3 prior tumor-directed surgical procedures, at least 1 prior irradiation, and at least 1 prior chemotherapy regimen. Additionally, all patients had presumed pediatric biology of their tumors.

A 19-year-old female patient enrolled on arm A was diagnosed with WHO grade III localized anaplastic astrocytoma. She had 1.95 x 109 total nucleated cells manufactured and 1.87 x 109 EGFRt+ CAR T cells manufactured. She received 6 doses of treatment.

Both patients enrolled on arm B were males with WHO grade III metastatic ependymoma. The first, a 16-year-old, had 3.2 x 109 total nucleated cells manufactured, 2.97 x 109 EGFRt+ CAR T cells manufactured, and received 9 doses of treatment. The second patient, aged 26, had 2.06 x 109 total nucleated cells manufactured, 1.87 x 109 EGFRt+ CAR T cells manufactured, and received 9 doses of treatment. The latter patients product in arm B had initial failure of viability screening, but with 2 additional manufacturing attempts, enough CAR T cells were generated to complete a minimum of 2 treatment courses.

The study was designed to primarily assess feasibility, safety, and tolerability, with assessment of CAR T-cell distribution and disease response as secondary objectives.

Patients experienced post-treatment symptoms. One patient who underwent imaging experienced radiographic evidence of treatment-mediated localized CNS immune activation.

Additional results showed that the most common adverse effects (AEs) observed in all patients were headache, pain at metastatic sites of spinal cord disease, and transient worsening of a baseline neurologic deficit. Additionally, the 2 patients on arm B experienced fever within 24 hours following infusion. These AEs were deemed possibly, probably, or definitely related to CAR T-cell therapy.

Systemic C-reactive protein elevation was also noted in all patients and overlapped with the timing of headaches and/or pain.

Regarding CSF cytokines and radiographic imaging, CAR T cells were not detected in any patient at any time point following infusion in CSF via flow cytometry or in peripheral blood via quantitative polymerase chain reaction. NonCAR T cell populations of CD4+ and CD8+ T cells were detected in CSF after infusion.

Cytokines, including CXCL10, CCL2, granulocyte colonystimulating factor, granulocyte-macrophage colony-stimulating factor, IFN2, IL-10, IL12-p70, IL-15, IL1, IL-6, IL-7, and tumor necrosis factor, were detected in the CSF following infusion. One patient also had elevated VEGF.

Additional studies are planned to evaluate the relationship between target antigen density and clinical toxicity and response.

With these findings, the trial is planned to enroll the broader age cohort of patients aged 1 to 26 years. Notably, the trial will include patients with diffuse midline glioma.

Two additional studies are also planned. BrainChild-02 (NCT03638167) will deliver EGFR-specific CAR T cells to pediatric patients with recurrent or refractory EGFR-positive CNS tumors. BrainChild-03 (NCT04185038) will deliver B7-H3specific CAR T cells to pediatric patients with recurrent or refractory CNS tumors or diffuse intrinsic pontine glioma.

Gleaning the results of all 3 BrainChild studies, the investigators plan to use a multiplexed strategy to overcome tumor heterogeneity, which remains a challenge for drug development in this patient population, and antigen escape.

Ultimately, the experience of the initial three patients treated on BrainChild-01 suggests that repeated locoregional HER2-specific CAR T-cell dosing might be feasible and that correlative CSF markers might be valuable in assessing on-target CAR T-cell activity in the CNS, concluded Vitanza and coauthors.

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HER2-Specific CAR T Cells Induce Early Efficacy Without Dose-Limiting Toxicities in Pediatric CNS Tumors - OncLive

The future is quite bright for multiple myeloma. We are really homing in on the best regimen for frontline therapy in transplant-eligible and -ineligible [patient populations], Martin said. We are also closer with our recommendations to figuring out how to treat early-relapsed multiple myeloma. We have a variety of novel drugs that are approved for use to treat [patients with] late relapse. That [setting] has been our unmet medical need, [historically].

Martin, a clinical professor of medicine in the Adult Leukemia and Bone Marrow Transplantation Program; associate director of the Myeloma Program; and co-leader of the Cancer Immunology and Immunotherapy Program at the Helen Diller Family Comprehensive Cancer Center of the University of California, San Francisco; added that there are several very exciting therapies under investigation in clinical trials, including BiTEs. [These therapies] are showing unprecedented responses in very refractory patients, [including] the triple-class exposed patients, which is amazing.

He spoke with OncLive during an Institutional Perspectives in Cancer webinar on multiple myeloma. He chaired the virtual meeting which covered updates in frontline, early-, and late-relapsed multiple myeloma, immunotherapy in multiple myeloma, and frontline and relapsed/refractory amyloidosis.

Martin discussed the latest news in frontline, early relapsed, and heavily pretreated multiple myeloma, including the growing promise of quadruplets, emerging targets beyond BCMA, and the potential emergence of quadruplets, venetoclax (Venclexta), and antiviral therapy in amyloidosis.

Martin: For frontline therapy in multiple myeloma, we break [our algorithm] up [according to] patients who are fit and [unfit. Patients who are fit] can likely go to stem cell transplant. A quadruplet is going to be where we are headed, and it is going to be [a quadruplet using] the 3 different classes of drugs: a monoclonal antibody, an immunomodulatory drug [IMiD], and a proteasome inhibitor [PI], together with a steroid. [The combination of] those 4 classes of drugs [were evaluated] in the GRIFFIN [NCT02874742] and Cassiopeia trials [NCT02541383]. The GRIFFIN trial looked at daratumumab [Darzalex], lenalidomide [Revlimid], bortezomib [Velcade], and dexamethasone, whereas the Cassiopeia trial looked at daratumumab, thalidomide [Thalomid], and dexamethasone. Both [trials] showed spectacular early responses for induction therapy to [the respective] quadruplets.

Another study looked at daratumumab [plus] carfilzomib [Kyprolis], lenalidomide, and dexamethasone [KRd]. That trial too showed unprecedented early responses as frontline therapy. More studies are looking at other CD38[-directed monoclonal antibodies], like isatuximab-irfc [Sarclisa], together with lenalidomide, as well as KRd.

These quadruplets are showing fast and deep responses after 4 cycles [of treatment]. For patients who are transplant eligible, [treatment with a quadruplet] prepares them for transplant quite well. They can go into transplant with a nice, deep response and, hopefully, [derive] a deeper response after remission.

The question exists of whether the quadruplets and other therapies may take away the need for autologous stem cell transplant. Right now, transplant is still part of frontline therapy and is especially useful in patients who have high-risk disease.

In the transplant-ineligible population, the MAIA trial [NCT02252172] looked at daratumumab plus lenalidomide and dexamethasone vs lenalidomide and dexamethasone. The triplet has shown a median progression-free survival [PFS] approaching 60 months; that is just amazing for frontline therapy. We will see if quadruplets are needed in the transplant-ineligible setting.

We have several trials testing quadruplet therapy in the transplant-eligible population. Both daratumumab and isatuximab are being combined with IMiDs, PIs, and dexamethasone in a randomized fashion [vs triplet therapy]. We will see what the winner is. It will be interesting as we move forward, but right now, if we start that triplet therapy, we expect a PFS of 60 months, which is just amazing.

When we think about early relapse, what becomes important is what patients were on when they became relapsed or refractory. If they were on an IMiD, most of the time it was lenalidomide as maintenance therapy. We would then consider that patient lenalidomide refractory. In that scenario, we would use a CD38[-directed monoclonal antibody] plus pomalidomide [Pomalyst] and dexamethasone or a CD38[-directed monoclonal antibody] plus a PI and dexamethasone.

The data with daratumumab plus pomalidomide and dexamethasone, as well as isatuximab plus pomalidomide and dexamethasone, are quite good. Truthfully, my favorite [approach] is that if the patient is on an IMiD, I give an antibody together with a PI. The IKEMA [NCT03275285] and CANDOR [NCT03158688] studies have shown deep and durable responses with a CD38[-directed monoclonal antibody] plus carfilzomib and dexamethasone in the early-relapsed setting.

The CANDOR study showed a PFS of about 28 months. We still need longer follow-up from the IKEMA study to see what the PFS is going to be, but it is certainly going to be at least 28 months. Specifically, [in the IKEMA] study we showed that 30% of patients had achieved minimal residual disease [MRD] negativity with the triplet combination in the early-relapsed setting. Its unprecedented to see these deep responses with evidence of MRD negativity.

If patients have not received a CD38[-directed monoclonal antibody] as part of frontline therapy, that is what the first component should be to add for first relapse. The other regimens, which weve used before and are good, include pomalidomide, bortezomib, and dexamethasone, or pomalidomide, carfilzomib, and dexamethasone. There are multiple other choices, but those are my favorites.

In early-to-mid relapse, we usually use a ping-pong approach where we go back and forth between the categories of agents. Eventually, after 2 or 3 lines of therapy, patients have been exposed to what I call the big 5, which are lenalidomide, bortezomib, carfilzomib, pomalidomide, and a CD38-directed antibody. This is a setting which had been our unmet medical need.

We now have 3 agents that are FDA approved for that group of patients. We have selinexor [Xpovio] plus dexamethasone, which was approved based on the STORM trial [NCT02336815]. That doublet can be used in the [originally indicated] twice-weekly [dose], or given once weekly, which is much better tolerated. Often, we combine [selinexor] with another agent, such as bortezomib, carfilzomib, pomalidomide, or, even, daratumumab, so it is a kind of pick-your-partner [agent] in that regard. There are toxicities associated with selinexor, and we must follow patients closely. We cant just give them the therapy and see them in 4 weeks. We must follow their sodium closely because some patients need salt replacement, hydration, and anti-emetics.

The second [agent approved for triple-class refractory multiple myeloma] is belantamab mafodotin-blmf [Blenrep], which is an antibody-drug conjugate that targets BCMA. The poison is MMAF, which is associated with thrombocytopenia and ocular toxicity. We found that when belantamab mafodotin is used as a single agent without a steroid, the response rate was just over 30%. Patients who respond have durable responses upward of 10 or 12 months. We just have to watch patients for ocular toxicity because [belantamab mafodotin] can cause keratitis on the surface of the eye. Patients must see an ophthalmologist before each dose of belantamab mafodotin, which is dosed every 3 weeks. In my experience, [keratitis] usually occurs after the second or third dose. Most patients respond after the first or second dose, so we can see if the patient responds, and then continue or modify the regimen. We can lengthen the dose out to every 4 weeks or every 6 weeks or drop the dose from 2.5 mg/kg to 1.9 mg/kg.

Lastly, we have a new drug called melphalan flufenamide [melflufen; Pepaxto], which is a lipophilic, alkylator-based therapy. The lipophilic component gets the drug fast into cells, but it can be cleaved off the alkylator by aminopeptidases. In fact, normal cells dont have many aminopeptidases, so [melflufen] gets in and out of normal cells relatively quickly; however, the drug gets in myeloma cells, the lipophilic component is cleaved off, and the alkylator gets trapped inside the cell. [Melflufen] is [administered as] one flat dose of 40 mg every 4 weeks with weekly dexamethasone. It is tolerable; the big adverse effect [AE] is blood count suppression. Weve seen response rates in the 25% to 30% range.

The newest [therapy] on the block in what is available for patients who have had 4 prior lines of therapy is the CAR T-cell therapy ide-cel. It is BCMA directed, the original vector was known as bb2121. It is now FDA approved.

The rollout [of ide-cel] has been a little slow in terms of slot allocation, and it has been difficult for centers across the country to get patients on slots. We are hoping that the slot availability will increase over the next few months.

That said, for patients who are triple-class refractory and have had 4 prior lines of therapy, [ide-cel] is a perfect therapy. The CAR T cells have to be done at a licensed CAR T-cell center, of which there are only about 70 in the United States. That comes with some overhead because patients must move to the center and remain there for the first 30 days of therapy because of the significant toxicities associated with CAR T-cell therapy. [These AEs] are mostly cytokine release syndrome [CRS], which happens 80% to 90% of the time, and some neurotoxicity, which is reported in around 15% to 20% of patients. Patients must be followed closely and require initial hospitalization between 7 to 14 days. Then, patients must stay local [for follow-up].

There is a lot of overhead, but it is a one-and-done treatment. We collect their T cells, give them lymphodepletion, give them back the T cells, and patients are off therapy. The median PFS for ide-cel is about 12 months, so hopefully patients get 12 months of free time where they dont need therapy and have truly good quality of life, which is quite nice.

The nice thing about immunotherapy is that multiple targets are being investigated. BCMA was our first target, but we have others, such as GPRC5D and FcRH5. We have multiple different CAR T-cell therapies currently in research studies to try to build upon ide-cel.

We also have BiTEs, in which one arm binds to BCMA or whatever the target is on the myeloma cell, and the other arm looks for the immune cell in the local environment. Most of the other arms bind to CD3 on T cells to activate the T cells. [BiTEs] are a little bit different in terms of how they bind to the myeloma cell and how much they activate the T cell by binding to CD3.

That said, in the early research, most of these therapeutics as single agents have shown response rates on the order of 60% to 80%. Thats, again, unprecedented for single agents. These therapeutics are quite impressive in terms of response rates, but they are also associated with CRS and mild neurotoxicity. They require initial dosing in the hospital and patients are usually hospitalized for 7 to 10 days for step-up dosing. After that, [treatment] can be done in the outpatient setting with intermittent dosing. BiTEs vary from dosing weekly and then less frequently to every 3 weeks. Coming back to the center every 3 weeks is reasonable, even for patients who live outside the research center.

In San Francisco, we have patients coming in every 3 weeks to get their therapy and then they head back home, which is nice. However, it is ongoing therapy and patients must continue their therapy rather than receive a one-and-done treatment. This is because BiTEs are off-the-shelf products. There is not a collection and manufacturing step. These drugs are going to be given in the community eventually once they are approved. These drugs will be used in many more patients compared with CAR T-cell therapy just because of the logistics of CAR T-cell therapies, so BiTEs are exciting.

These advances [observed in multiple myeloma] have also spilled over to amyloidosis. We now have great frontline therapy for amyloidosis, as well as many irons in the fire [evaluating] ways we can treat relapsed amyloidosis. Weve had a troubled past [with] antiviral therapy in amyloidosis. However, there is renewed interest in this and, certainly, there are patients with amyloidosis who would benefit from antiviral therapy.

There is a lot of work going on in amyloidosis currently. The ANDROMEDA study [NCT03201965] has shown in randomized fashion that daratumumab plus bortezomib, cyclophosphamide, and dexamethasone [VCd] results in better organ response rates and PFS vs VCd alone, which had really been our standard therapy in amyloidosis. Going forward, patients with amyloidosis should receive this quadruplet as frontline therapy.

Patients with amyloidosis also have a high incidence of 11;14 translocations [t11;14]. Some case reports [have read out] of patients being treated with venetoclax. Ongoing research avenues are going to further investigate venetoclax with or without the combination of other drugs. Venetoclax will have a strong response rate in patients with amyloidosis and will be used for initial relapse. Eventually, [venetoclax] might be used in patients with t11;14, but those studies are being done. Approval for that is a long way down the road.

Also down the road for amyloidosis are BiTEs. BCMA is on the surface of plasma cells in amyloidosis, also, [as in multiple myeloma]. There is also a renewed interest in antiviral therapy in amyloidosis. The amyloid proteins deposit in the cell and cause significant organ toxicity, especially in the [heart] and kidneys. Antiviral therapy may enhance and quicken organ responses to improve survival for patients, including those with severe cardiac amyloidosis.

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Emerging Quadruplets, Novel Targets, and Immunotherapy Advances Personalized Medicine in Multiple Myeloma - OncLive

Mr. Paul Wilson, Consultant General Surgeon, successfully completes complex hernia repair with minimally invasive approach Mr. Paul Wilson, Consultant General Surgeon, successfully completes complex hernia repair with minimally invasive approach

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NHS Surgeon First in Europe to Implant TELA Bio's OviTex® LPR Reinforced Tissue Matrix

- On Monday, July 26th, New Clinical Data for SavaDx to be Shared ina Poster Presentation -

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Cassava Sciences to Present New Clinical Dataset at 2021 Alzheimer’s Association International Conference

CAMBRIDGE, Mass., July 21, 2021 (GLOBE NEWSWIRE) -- Vericel Corporation (NASDAQ:VCEL), a leader in advanced therapies for the sports medicine and severe burn care markets, today announced the following webcast and conference call to discuss its second-quarter 2021 financial results and business highlights.

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Vericel to Report Second-Quarter 2021 Financial Results on August 4, 2021

LA JOLLA, Calif., July 21, 2021 (GLOBE NEWSWIRE) -- Artelo Biosciences, Inc. (NASDAQ: ARTL), a clinical stage biopharmaceutical company focused on the development of therapeutics that target lipid signaling pathways, including the endocannabinoid system, today announced that Ladenburg Thalmann & Co. Inc. will host an R&D showcase focused on the Phase 1b/2a Cancer Appetite Recovery Study (“CAReS”), evaluating the Company’s lead drug candidate, ART27.13. The webinar will be hosted by Michael Higgins, Managing Director and Senior Biopharmaceutical Equity Research Analyst on July 28th, 2021 at 1pm EDT/10am PDT. This event will include the lead investigator on the CAReS study, Barry Laird, PhD, a Senior Clinical Consultant of Palliative Medicine at St Columba's Hospice Care in Edinburg, UK. Among a number of key topics, Dr. Laird will be discussing the etiology of anorexia and the accompanying challenges of effectively treating anorexia.

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Ladenburg Thalmann to Host R&D Showcase Featuring Artelo Biosciences’ CAReS Study on July 28, 2021

LEXEO obtains exclusive rights to three investigational AAV-mediated gene therapy programs for rare cardiac disorders, all of which have no existing disease-modifying treatments available

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LEXEO Therapeutics Expands Cardiac Gene Therapy Pipeline with Acquisition of Stelios Therapeutics and its Gene Therapy Programs for Rare...

NEW YORK, NY, July 21, 2021 (GLOBE NEWSWIRE) -- via NewMediaWire -- Tauriga Sciences, Inc. (OTCQB: TAUG) (“Tauriga” or the “Company”), a New York based diversified Life Sciences Company, today announced that it has commenced sales of its Tauri-Gum™ product line in the United Kingdom.  In addition, the Company has retained a full-time salesperson - located in London. The Company expects to substantially increase its sales, in the United Kingdom, throughout the remainder of Calendar Year 2021 and beyond.

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Tauriga Sciences Inc. Commences Sales of its Tauri-Gum Product Line in the United Kingdom

EMERYVILLE, Calif., July 21, 2021 (GLOBE NEWSWIRE) -- Berkeley Lights, Inc. (Nasdaq: BLI) today announced a strategic collaboration with Thermo Fisher Scientific aimed at addressing challenges in commercial-scale viral vector manufacturing. The partnership, which began in December of 2020, brings together Berkeley Lights’ leadership in functional biology characterization with Thermo Fisher’s expertise in viral vector manufacturing and analytics. Together, the companies are collaborating on a next-generation workflow using the Berkeley Lights Platform to accelerate and improve the development of stable AAV (Adeno-Associated Viral) and LV (Lentiviral) vector producer cell lines.

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Berkeley Lights announces technology collaboration to accelerate and improve gene therapy viral vector development and manufacturing

NEWPORT, United Kingdom and AMSTERDAM, July 21, 2021 (GLOBE NEWSWIRE) -- Nanopharm Ltd., an Aptar Pharma company and leader in contract research and development of orally inhaled and nasally delivered drug products (OINDP) and Leyden Labs, a company targeting commonalities of viral families to protect humanity from known and future viruses, today announced that they have entered into an agreement to develop nasal sprays that may provide broad protection against respiratory viruses, combining Leyden Labs’ portfolio and Nanopharm’s expertise in the development of nasally delivered drug products.

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Nanopharm and Leyden Labs Announce Agreement to Develop Intranasal Spray Product Candidates for Prophylactic Use Against Known and New Respiratory...