Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood. The two most common fungal infections that affect people with AML are aspergillosis and candidiasis.

Invasive fungal infection is a leading cause of illness and mortality in people with acute leukemia. According to a 2019 study, about 12 to 24 percent of people with AML develop invasive fungal infections. But there are medications to prevent and treat these fungal infections.

Read on to find out how AML lowers resistance to fungal infection, as well as prevention and treatment strategies.

AML is a type of blood cancer. It starts in the bone marrow but usually moves into the blood fairly quickly. It tends to develop from white blood cells that dont function as they should.

White blood cells are a vital part of the immune system. When a foreign invader like bacteria, virus, or fungus enters your body, white blood cells spring into action. Their job is to attack the invader and prevent illness.

When you have AML, leukemia cells crowd out healthy white blood cells. The production of new white blood cells becomes impaired.

In addition, treatment for AML involves intense chemotherapy, which can also lower your white blood cell count. As a result, the immune system is suppressed and youre more vulnerable to infection and illness.

Other treatments that can weaken the immune system include:

Other health problems and nutritional deficiencies can also contribute to the suppression of the immune system.

During cancer treatment, your doctor will monitor your white blood cell count, particularly a type of white blood cell called neutrophils. Theyre an important line of defense against infection. If your neutrophil count is low, you have a condition called neutropenia, which increases the risk of infection.

Aspergillus molds and Candida yeasts are the most common fungi to affect people with AML.

Aspergillosis is an infection triggered by Aspergillus. Its a common mold that can be found indoors or outside. Most of us breathe it in every day without cause for concern. But if you have a weakened immune system, you have an increased likelihood of developing the illness.

There are different types of aspergillosis, each causing a different set of symptoms:

While its possible to develop any of these types if you have a weakened immune system, about 10 percent of people with AML develop invasive aspergillosis. This infection most commonly affects the lung.

Candidiasis is an infection caused by Candida. We all have this yeast on our bodies. It only causes problems when it grows out of control or enters the bloodstream or internal organs.

Different types of candidiasis cause different symptoms:

Invasive candidiasis is a serious infection that can affect many parts of the body. In addition to causing fever and chills, invasive candidiasis can affect the:

Some less common types of fungi that can also affect people with AML are:

Fungi are everywhere, so its difficult to completely avoid them. Here are a few things you can do to help lower your risk of infection:

Prevention and treatment for fungal infections in people with AML require an individualized approach. Even if you show no sign of infection, your doctor may prescribe a prophylactic medication designed to prevent a fungal infection. They include:

If you do develop a fungal infection, some drugs above can help treat it. Additional medications used to treat fungal infection are:

Fungal infections can recur. Thats why you may need both antifungal therapy and prophylactic therapy until your blood counts improve.

Medications to prevent or treat fungal infections each have potential benefits and risks. The treatment that is best for you depends on a number of factors, such as:

Symptoms of fungal infections are similar to those of other health conditions. Its a good idea to get in touch with your doctor whenever you have new or worsening symptoms. While some fungal infections are minor, others can be life threatening.

Untreated, fungal infections can spread to other parts of the body. Getting a quick diagnosis means you can start treatment that may prevent illness. Some signs of fungal infection include:

Fungal infections are not uncommon in people with AML. Both AML and chemotherapy can significantly weaken the immune system, increasing risk for infection. Fungal infections can affect a single organ, such as the lungs or sinuses, or they can affect the bloodstream and multiple organs.

Aspergillosis and candidiasis are the most common fungal infections affecting people with AML.

Fortunately, there are medications to help prevent and treat fungal infections. If you have AML, speak with your doctor about your risk factors and how you can prevent fungal infection.

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Acute Myeloid Leukemia Fungal Infections: Types and Treatment - Healthline

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Myelodysplastic syndromes, known commonly as MDS, are a group of bone marrow diseases characterized by bone marrow failure, or an inadequate production of blood counts called cytopenia.

In a presentation at the CURE Educated Patient Leukemia Summit, Dr. Rami Komrokji, section head for Leukemia and MDS and Vice Chair of the Department of Malignant Hematology at Moffit Cancer Center, gave a run down on the diagnosis and staging process for MDS.

Diagnosing MDS

Komrokji explained that the myelo- prefix means bone marrow, and -dysplasia means abnormal-looking cells. When a patient has cytopenia, they may experience certain symptoms.

If patient is anemic, they will have shortness of breath, fatigue, palpitations, said Komrokji in an interview with CURE. If they have low platelets, they will have bleeding tendency, bruising. If they have low white blood cell counts, they will have maybe infections. So usually, either some of those symptoms will prompt blood testing, or on routine physical exam, the patients are found to have low blood counts. So that's usually the initial step.

Doctors will usually look into nutritional deficiencies such as B12, folate and ferritin, said Komrokji. Eventually, the patients will get a bone marrow aspirate and biopsy to diagnose their disease, which includes several parts.

There is the morphologic part, which means the pathologists are looking at the cells under a microscope, explained Komrokji. And then there is also some genetic testing. We look at cytogenetics nowadays, we look at gene mutations. So we put all of this information together to make the diagnosis.

The hematopathologist must see dysplasia, increased myeloblasts (immature cells known as blasts within the bone marrow) or certain cytogenetic abnormalities to make their diagnosis, Komrokji said.

Sometimes the diagnosis is straightforward, but sometimes it could be challenging, he added. It truly depends on an experienced hematopathologist to make the diagnosis.

Staging and Risk Stratification

Once a patient receives an MDS diagnosis, their doctor will go over risk stratification, or understanding what the risk of their disease is, which is what they consider staging, Komrokji said.

Now in MDS, its not like a lung cancer or colon cancer, he said. The disease does not spread around. The staging is based on the blood counts, on the percentage of those myeloblasts or immature cells (and) the chromosomal makeup of the cells. And nowadays, we sometimes also incorporate the presence of gene mis-happenings as well. So we get a lump score to estimate the risk.

Doctors typically use the International Prognostic Scoring System (IPSS) to categorize patients into one of five categories very low, low, intermediate, high and very high. The risk is the impact on survival and whether the disease will transform to leukemia, Komrokji explained. The disease risk must be known in order to tailor the patients treatment to them.

I always advise patients to see a specialized center in MDS, because obviously, those are not that common diseases, he said. A community oncologist could see a few (cases) per year, while an experienced center like in our place, we see like 15 to 20 per week.

Gene Mutations

Komrokji said that understanding gene mutations is an evolving field that is slowly becoming routine.

I advise all patients to inquire if theyve gotten genetic testing or not, he said. This sort of testing will help them understand any abnormalities. Doctors can look at a patients individual gene levels and detect for mutations, of which at least one was identified in 90% of patients with MDS.

Understanding the patients mutation(s) helps them tell whether there is a clonal hematopoiesis or mis-happening that occurred. It can also impact prognosis and allow them to further understand the disease risk.

And finally, some of them are targetable or important to follow through the treatment, said Komrokji. So patients should probably definitely have a genetic testing done. And sometimes after a treatment failure, we repeat it because we see other mutations that we could target with new drugs.

What Causes MDS?

In most cases, the cause of a patients MDS diagnosis is unknown.

We think it's phenomena of senescence or aging of those stem cells in the bone marrow that produces the blood, said Komrokji. Obviously, the process is very complicated. We have billions and billions of cells divide billions of times a day. So you know, as those cells age, mistakes can happen in them.

In most cases, he said, the mis-happenings which lead to the disease are random and at no fault of the patient. It is extremely rare for MDS to be inherited through familial genes.

There are, however, several known risk factors of MDS. If someone has history of another form of cancer and has received chemotherapy or radiation therapy, they may have possible stem cell damage and can develop MDS this is called therapy-related MDS. There has also been association of the disease with benzene exposure, chemical exposure and radiation exposure. Patients who have connective tissue diseases such as rheumatoid arthritis and lupus are at a slightly higher risk of getting MDS due to inflammation in the body and certain medications used to treat those diseases.

I would say there's a lot of better understanding of the disease in the past several years, of genetic mutation testing and incorporating them in practice, Komrokji said. And I think, you know, there are a lot of new treatments on the horizon for patients; there are several clinical trials in advanced phase.

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The Basics of MDS: Diagnosis and Staging - Curetoday.com

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DetailsCategory: DNA RNA and CellsPublished on Tuesday, 03 August 2021 10:03Hits: 951

Off-the-Shelf CAR T-cell Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

Phase 1 Clinical Study will Evaluate Three Dosing Regimens of FT819 for Patients with Advanced B-cell Leukemias and Lymphomas

SAN DIEGO, CA, USA I August 02, 2021 I Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, announced today that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement.

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics haslicensedintellectual propertyfrom MSK on which Dr. Sadelain is aninventor.As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

SOURCE: Fate Therapeutics

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Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of FT819, the First-ever iPSC-derived CAR T-Cell Therapy |...

Bone Marrow Stem Cells Comments Off on Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of FT819, the First-ever iPSC-derived CAR T-Cell Therapy |… | August 6th, 2021

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

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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

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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

Skin Stem Cells Comments Off on Stemson Therapeutics Secures $15M Series A Funding to Cure Hair Loss – Business Wire | July 22nd, 2021

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

Skin Stem Cells Comments Off on Learn how to remove unwanted fat with procedures beyond liposuction – ABC 4 | July 22nd, 2021

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

Skin Stem Cells Comments Off on What sets blood cancers apart from other cancers? | Lifestyles | washtimesherald.com – Washington Times Herald | July 22nd, 2021

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

IPS Cell Therapy Comments Off on Base Editing as Therapy for Common Inherited Lung and Liver Disease Shows Promise – Clinical OMICs News | July 22nd, 2021

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

Spinal Cord Stem Cells Comments Off on Stemming the tide of stem-cell treatment scams – Houston Chronicle | July 22nd, 2021

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

Spinal Cord Stem Cells Comments Off on IU School of Medicine researchers discover new potential for functional recovery after spinal cord injury – Spinal News International | July 22nd, 2021

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.

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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

Spinal Cord Stem Cells Comments Off on Introducing the 3D bioprinted neural tissues with the potential to ‘cure’ human paralysis – 3D Printing Industry | July 22nd, 2021

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

Spinal Cord Stem Cells Comments Off on Mesenchymal Stem Cells Market Witnesses Upward Trend with High Prevalence of Parkinson’s Disease The Manomet Current – The Manomet Current | July 22nd, 2021

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.

Read the original here:
HER2-Specific CAR T Cells Induce Early Efficacy Without Dose-Limiting Toxicities in Pediatric CNS Tumors - OncLive

Spinal Cord Stem Cells Comments Off on HER2-Specific CAR T Cells Induce Early Efficacy Without Dose-Limiting Toxicities in Pediatric CNS Tumors – OncLive | July 22nd, 2021

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.

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

Cardiac Stem Cells Comments Off on Emerging Quadruplets, Novel Targets, and Immunotherapy Advances Personalized Medicine in Multiple Myeloma – OncLive | July 22nd, 2021

After a year under the hatch, this summer 2021, glowing, luminous and radiant is the go-to gorgeous look that American women want !

For whatever face you have to show the world today, moisturizing oil replenishes your skin, repairing damage from UV and boosting your natural glow with an astonishing amount of benefits- which is formulated to re-energize your look as it tones and refines pores. Many viewers have asked my expert advice on the best ways to approach and achieve a dewy summer complexion that will leave skin luminously smooth on the path to corporate ascension during business hours as well as summer social activities.

In the summer, I can simply suggest that less is more. Radiant glow is the way to go with a delicate added dose of a real-to-the-feel modified bronzer and a fresh coral blush. This season, in addition to eating fruits and vegetables. drink lots of water to replenish the skin. Be mindful to get in a sweaty cardio sesh to increase blood flow and that healthy look from within which ultimately surfaces in the face to improve skin texture and tone for a natural radiant complexion.

Protect your skin from the sun:

As I mentioned earlier, I know everyone just wants to get out and see the world again but you must take protection from the sun. Bronzing face drops is your answer to a bronzed face without the risks of sun exposure. Integrated into your skincare routine your tan can now be customizable, buildable, and most importantly, fake, without looking fake.

Exfoliation is essential for smoothskin. I recommend to exfoliate once or twice a week to remove deadskincells and leaveskin glowing. This season, a unique blend of supercharged ingredients have been expertly formulated to deeply moisturize and restore the skins natural balance, revealing a clear and radiant glow.

If you're looking for a moisturizer with a luminous finish, then read below where I have curated a Forbes list of super-hydrating product offerings infused withtechnicall advanced hyaluronic acidand pearl articlesthat blur, reflect, and enhance your complexion to make you look instantly more radiant than ever!

+ Lux Unfiltered:

For a natural color and glow.

+ Lux UnfilteredNo.12 Bronzing Face Drops is your answer to a bronzed face without the risks of sun exposure. N12 seamlessly integrates into your skincare routine without disrupting your process or products. It is fragrance-free, non-comedogenic, compatible with all skin types, and loaded with antioxidants. Your tan is now customizable, buildable, and most importantly, fake, without looking fake. Recommended to mix with your desired number of drops with your face moisturizer and apply to clean skin.$42

AbsoluteJOI:

The new Daily Hydrating Moisturizing Cream is the first of its kind, a nutrient-rich 2-in-1 tinted ... [+] moisturizer specifically crafted for women of color for everyday use.

AbsoluteJOI-The new Daily Hydrating Moisturizing Cream is the first of its kind, a nutrient-rich 2-in-1 tinted moisturizer specifically crafted for women of color for everyday use. The Daily Hydrating Moisturizing Cream leaves no white cast a common problem for people with melanin-rich skin. $42.00

AJ Crimson Beauty:

AJC Universal Finishing Powder in Toasted Cinnamon

AJ Crimson Beauty-AJ Crimson Beauty's Universal Finishing Powders are perfect for all skin tones. Great to use to set your makeup for a Matte or Semi Matte Skin Finish. Can Be Used to set Foundation, Concealer, Contour, Highlight or Tattoo cover! Available in a range of colors including Neutral Matte, Bamboo, Rick Umber and Toasted Cinnamon. $35

Beauty Bakerie:

Swatches of the Beauty Bakerie InstaBake Aqua Glass Foundation in Shades 301N to 325N.

Beauty BakerieBeauty Bakerie always makes strides to be inclusive towards people of color and provides a wide shade range for all skin tones. Lack of darker shades in complexion products is a huge issue in the cosmetics industry, and Beauty Bakerie brings a revolutionary shade range to the table with the InstaBake Aqua Glass Foundation. The shades are listed from Dark to Light to put darker complexions first. $34.00

Bespoke:

Luxury CBD, but affordable for every budget.

Bespoke-Manuka Honey and Bespokes Potent CBD, infused in one amazing product with an astonishing amount of benefits. The Manuka Honey + CBD cream for hands and body offers you the healing benefits of Manuka honey, the inflammatory and pain support of CBD, plus the soothing, calming properties of menthol extract. Bespoke sources our Manuka honey from New Zealand. But not all Manuka is equal. We source only the purest honey with an Ultra Premium Grade Unique Manuka Factor (UMF) of 15+. Youre getting exceptionally high-quality Manuka along with the superior CBD youve come to trust Bespoke Extracts for. This topical treatment will enhance your skincare regimen. Use sparingly on sore, dry skin, or when experiencing muscle or joint pain. Manuka Honey + CBD Cream will nourish your skin and provide supportive care to soft tissues. $59

Circumference:

The gentle cleanser is powered by olive leaf extract, derived from byproduct harvested in California ... [+] that would otherwise go to waste.

Circumference- The second formula born from the Waste-NotSourcing Initiative - this Daily Regenerative Gel Cleanser is powered by upcycled olive leaves, in partnership with California-made, Brightland. Last fall, Circumference approached the modern essentials pantry brand to take the byproduct - that have no use in the olive oil making process - and slow-extract for bioactive nutrients. After the process was complete and the formula was perfected, mulch was returned to their farms for the following seasons compost - completing the circular economy.$48

CocoBaba:

CocoBaba Coconut Butter Mousse, Coconut Body Oil, and Coconut Oil Scrub.

CocoBaba- CocoBaba is the new all-natural, vegan skincare line for women founded by Emma Heming Willis. CocoBaba was originally conceptualized when Emma was pregnant with her first daughter and was in search for an all-natural coconut oil-based product line to nourish and soothe her skin but could not find one. After 4 years in the making, the brand finally launched earlier this year and while its targeted toward moms and moms-to-be, its great for anyone! As summer approaches and we spend more time outside, its time to pay extra attention to our skin and make sure its nourished and protected to maintain that beautiful summer glow all season long!

All CocoBaba products are made with pure, certified organic coconut oil, and are 100% vegan, dermatologically tested, and completely free of silicones, parabens, and mineral oils. The Coconut Butter Mousse is a natural, effective way to nourish skin with this whipped blend of coconut, chia, sunflower, and jojoba oil. The Coconut Body Oil is silky but never greasy, this natural beauty secret uses 100% raw certified organic coconut oil to lock in moisture. And finally, the Coconut Oil Scrub is an all-natural exfoliant made with real coconut husk and apple seed. $54.99

EiR NYC:

Surf Mud Body Oil

EiR NYC-As with all EiR suncare products, Surf Mud Body Oil is made with 100% Reef Safe Ingredients. Surf Mud Body Oil is a tinted tanning oil with Antioxidant-rich hydrating oil combined with zinc and chocolate to deeply moisturize and increase blood flow to the skin, and enhance your bronze-y sun-kissed look.$35

Elaluz:

Camila never leaves home without her All Day Beauty Water and neither should you keep your skin ... [+] glowing and give it a refreshing boost on-the-go all summer long!

Elaluz -When Elaluz founder Camila Coelho created The All Day Beauty Water she knew she wanted a versatile product she could use throughout the day to keep her skin glowing and nourished. Enriched with Brazilian superfood ingredients like Guarana & Papaya Extracts and Buriti & Bataua Oils, this instant skin boost is formulated to re-energize your look as it tones and refines pores. Use it before makeup to prep, post-application to set, or whenever you need an instant boost of radiance. $49 USD

Hey Dewy:

Get the cutest, facial humidifier today - your skin and hair will thank you for it.

Hey Dewy- Bring this portable USB humidifier with you wherever you go for continual hydration at your desk for work, overnight while you sleep or on-the-go to your dream destination. You can also nourish your skin with Hey Dewy before, after or even during your beauty routine. Our portable facial humidifier is our flagship product that is the foundation of our brand and purpose. It serves as the conduit to wellness via water and humidification, as well as the means to giving 10% to Clean Water initiatives like The Water Project. $39

Hydra Bloom:

Moonshine Coconut Illuminizer helps bring out your inner glow by adding a gorgeous highlight to your ... [+] cheekbones, eyes and decolletage.

Hydra Bloom-This skin perfector suits all skin tones. Made with Coconut and natural shimmering minerals and Vitamin E and Australian Flower Essences this illuminizer will have you glowing. $28.00

James Read Tan:

Tan Easy-to-apply and can be tailored to your liking perfect to achieve that faux post-vacation ... [+] tan while quarantining.

James Read Tan-Concentrated onthe-go multi-vitamin gel tanning drops that you can add to your SPF or moisturizer. Formulated with powerful antioxidants and Vitamin complexes combined with key anti-ageing skincare ingredients to gently brighten, smooth and tan your skin. Formulated to improve the skins natural defense against free radicals, stimulate collagen synthesis and gives you a natural looking glow. Enriched with Vitamin C, Hyaluronic Acid, Aloe Vera, Natural Caramel and self-tan for the ultimate glow.$33

Kura Skin:

Kura Skin

Kura Skin-Kura Skin curates clean, personalized skincare routines just for you. Kura analyzes your age, location, existing product usage, skin types and concerns through a proprietary, high-tech algorithm to build your own skincare routine. Designed for all genders and ethnicities, you wont end up with a drawer full of samples youll never touch, or worse, a product that irritates your skin. Kura only curates nontoxic, cruelty-free, nutrient-dense, effective indie brands for healthy, glowing skin.Individual products starting at $28

lilah b.:

Moisturize, balance and prime with lilah b.s Aglow Priming Oil

lilah b. -A three-in-one serum, moisturizer, and primer that can be worn alone or under makeup creating a smooth, flawless canvas for long-wear makeup application. Aglow Priming Oil is a fast-absorbing, silicone-free priming face oil that nourishes and hydrates skin. Formulated with a nutrient-rich trio of tamanu, jojoba and sweet almond oils to soften, smooth and comfort the skin. Infused with grape seed extract to help improve skin firmness and reduce fine lines and wrinkles. Enriched with purple tea extract to improve skin texture and tone for a natural radiant complexion. The perfect dose of nourishment to prep skin with an effortless glowing finish. $68

Luzern:

Hydrate, soothe and boost luminosity with Luzerns new Alpine Rose Glacial Serum Masque.

Luzern-Infused with precious Ruby Powder, stem cells from the treasured Alpine Rose, a proprietary peptide-ferment, and an abundance of moisture factors and nutrients, this unconventional nectar mask provides instant hydration and calm, leaving skin velvety soft, smooth, and luminous. $150

Madeca Derma:

Madeca Derma Revitalizing Overnight Sleeping Mask

Madeca Derma-This supercharged night mask powered by propolis that helps skin recover overnight for a more youthful look by morning. $27.99

MAKE:

Gently yet effectively cleanses to remove impurities while hydrating and balancing

MAKE Succulent Skin Gream-This serum weight facial cleanser, is a pH-balanced, sulfate-free universal gel that gently cleanses skin, effectively removing dirt, oil and impurities without stripping the skin of essential moisture. Supercharged with amino acid enriched surfactants that preserve the skin barrier. Also formulated with prickly pear, cactus, agave, niacinamide and sodium hyaluronate to provide nutrients. $24

Manna Kadar Cosmetics:

Light up your skin with an all over radiance with Sheer Glow

Manna Kadar Cosmetics-Manna Kadar Cosmetics shimmer lotion works with all skin tones. Mix with foundation, BB cream, or body lotion to create a dewy glow for that radiant and youthful look. Get that extra highlighter look applying to cheek bones and collar bones for a more pronounced look. $29

Miami Beach Bum:

Formulated with oregano, aloe and jojoba to give your skin a full reset.

Miami Beach Bum To our marine scientist founder, self-care means being active and around water. After constantly being in wet bathing suits she developed folliculitis on her bum and was unable to find a natural solution for it. Using her chemistry background, Ayssa crafted our signature Bum + Body Cream with the mission of bringing skin health to the forefront of self-care. Now with a full collection, each product has become an essential part of Ayssas personal ritual and we hope they can become a part of everyone's unique self-care ritual as well. $45

natureofthings:

natureofthings Clarifying Facial Polish combines the purifying action of a cleanser with the ... [+] resurfacing and glow-enhancing benefits of an exfoliant.

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This gift set is the ultimate recipe for silky, moisturized skindeeply nourishes, restores, ... [+] soothes and helps lock in moisture. A definite favourite for all skin types.

ObakkiObakki is a purpose-led lifestyle brand that connects people through handcrafted products and artisan ware. The Moisturizing Gift Set in Earthy Scent features a deeply moisturizing trio set of Nilotica Shea Butter, Whipped Shea Lotion and the Obakki Organic Sugar Scrub. The Earthy Scent is an invigorating blend of cedar, ho wood, and grapefruit, and is a definite favourite for all skin types. All Obakki skincare products feature 100% all-natural ingredients and never contain palm oils, artificial fragrance or colourants, parabens, sulfates, or animal products. $76 USD

One Ocean Beauty:

To use, close eyes and spray hydrating mist all over the face 3 times a day

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Original Hemp:

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PRESSOLOGY- PRESSOLOGYs GOLDEN HOUR is a multi-purpose botanical serum carefully formulated with an exclusive caliber of Ayurvedic ingredients to heal and enhance the skin's long-term health. GOLDEN HOUR is infused with seven USDA organic and vegan cold-pressed oils, making it a rich source of powerful antioxidants, vitamins, and minerals that work to restore, repair, protect, and hydrate the skin. It's packed with vitamins A, B-complex, C, D, E, and F to stimulate fibroblasts, reducing fine lines and wrinkles while correcting skin tone and texture. Naturally occurring minerals like copper, iron, and selenium work to reduce hyperpigmentation and neutralize free radical damage. This plant-based serum is suitable for all skin types and versatile enough to be applied on the scalp and cuticles to encourage strong hair and nails.$38.00

Pseudo Labs:

Accentuates and highlights the natural beauty of the face with the PHreckles Kit.

Pseudo LabsPHreckles is a vegan, hypoallergenic, gluten free, cruelty free & water resistant faux freckle cosmetic that accentuates and highlights the natural beauty of the face. PHreckles melts into skin and blends with your natural complexion with almost zero effort and washes away with your daily cleanser. PHreckles Kits include a 4.3 ml PHreckles fill, a faux leather pouch and a custom Pseudo Labs pick for perfect application.$38.00

ROEN:

REN products combine a fashion-forward, innovative, glamorous approach with clean, ethical, ... [+] high-performance ingredients.

ROEN -Celebrity Makeup Artist, Kate Synnott, curated this Mothers Day Limited Edition Set your mom will absolutely love. This rosy inspired set is perfect for the mom who gravitates towards warm and cool pink tones. The 11:11 Eyeshadow Palette consists of cool hero tones designed for everyday where; Situation (soft pink), Hashtag (taupe green), Ciao! (deep fuschia), Rosie (petal pink). The Kiss My Liquid Lip Balm in Remi is a glossy nude liquid lip balm that provides the high shine of a gloss and the benefits of a balm. Disco Eye is a universally flattering eyeshadow that can be worn alone or applied as a topper to elevate and enhance your favorite shadow. Lastly, their avocado oil infused CAKE Mascara is hydrating mascara that volumizes, lengthens and lifts. $100 ($125 value)

Smashbox:

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Summer Fridays:

A shimmering blend of nourishing oils that illuminates skin for a light, sunkissed glow and is ... [+] gently scented with a warm, summertime fragrance

View original post here:
Here's How To Get The Perfect Summer Skin Glow In 2021 - Forbes

Skin Stem Cells Comments Off on Here’s How To Get The Perfect Summer Skin Glow In 2021 – Forbes | July 7th, 2021

Keila Torres knew during a conference trip to Florida she was going to meet the woman who saved her life. What she didn't expect was to see someone so familiar.

Torres, 44,of Worcester, Massachusetts,desperately needed a bone marrow transplant in 2016, when she was 39, to beatacute myeloid leukemia, a cancerthat starts in the bone marrow but often moves into the blood.

A bone marrow transplant isa treatment option for people withblood cancers, such as leukemia, and it replacesunhealthy blood-forming cells with healthy ones from a donor, according to Be The Match, a nonprofit that pairs peoplewith a donor.

She had slightly less than a 50% chance, according to Be The Match. But she beat thoseodds, thanks to Palm Desert resident Odalis Trinidad.

When the two women met on June 23, Torreshad a realization. Her body had been changing since the transplant, and now it started to make sense.

"My blood type changed to Odalis blood type.I developed allergies after the transplant, and she has allergies," Torres said. "Her hair is long, beautiful and really curly, and when my hair started to grow back, it was very curly, very tight curls. When I saw her, I was like, 'Wow, that's why my hair is like that.'"

"You basically become your donor. She lives in me," she added.

Dr. Ayad Hamdan, a bone marrow transplant specialist and board certified hematologist with the Eisenhower Lucy Curci Cancer Center, explained that since new stem cells from adonor replace the stem cells in a patients bone marrow, which is the "factory of our blood cells," the patient will have the same blood type as the donor.

He added it is possible for patients to develop allergies, and"most patients who receive chemotherapy or a transplant have the experience that their hair may grow back with a different texture," but the hair follicles themselves don't change.

Not only do the two women share hair textures and occasionally stuffy noses, they're driven by their desire to inspire others to help those in need.

Most 19-year-oldsare focused on having good times with their friends, not necessarily providing life-saving donations.

Trinidadsaid she tried to donate blood as often as she could, even though the process was always a bit uncomfortable either her arm would stop pumping enough blood, or her arm would be too sensitive. During one of her visits, she noticed a poster for Be The Match and decided to do some more research.

The process to join the donor registryseemed "really easy" for Trinidad, now 24.She received a registration kit to give a swab of cheek cells and sent it back in October 2015. Then camethe waiting period.

"If you get called, you get called; if you don't, well, at least you tried, right?" the Palm Desert resident said.

People between the ages of 18 and 44 can join the Be The Match donor registry. Cells from younger donors have the best chance of successful donations, according to the Mayo Clinic.

Due to a lack of diversity on the donor registry, white patients have a better chance of finding a match on the registry than do people of other races. According to the site, African Americans have a 29% chance, Asians and Pacific Islanders 47%, Latinos 48%, Native Americans 60% and whites 79%.

In July 2015, Torres, 38 at the time, learned she was diagnosed with Stage 3 breast cancer. With two young sons, ages 15 months and 5 years old at the time, she knew she had to fight to be there for her boys. After chemotherapy, radiation, lymph node removal and a bilateral mastectomy, she was declared cancer-free a year later.

The good news, unfortunately, was spoiled in September 2016.

"I felt like I was fine. I was recovering, I was spending time with my kids, I was going to work, my hair was growing back and I felt great," Torres said. While undergoing a bone marrow biopsy, she was told "there was something wrong" with routine lab work.She remembered asking her oncologist, "What's the worst that could happen?"

"If we find leukemia," Torres recalled her oncologist saying. "When I heard leukemia, I was like, 'Oh,that's not going to be me, it's probably something else.'"

But the biopsy showed she hadacute myeloid leukemia. It isa common type of leukemia in adults, although it accounts for just 1% of all cancers,according to Cancer.org.It is also generally uncommon to find in people younger than 45. Torres was 39.

"I was in shock. I was devastated. I had already gone through so many things," Torres said, "but in the back of my head I was thinking, 'I've been through breast cancer, I can do this.'"

But the gravity of the situation didn't hit her until she met the leukemia team at Massachusetts General Hospital. Walking into one of the clinic rooms, she remembers feeling "very claustrophobic,"like she was "running out of breath."

Torres began chemotherapy atMassachusetts General, but to have a betterchance at beating leukemia, she would need a bone marrow transplant.

The two women had plenty in common even before the transplant,Torres said, almost as if Trinidad was always her"missing puzzle piece." They both have birthdays in October, mothers from Guatemala (Torres grew up there as well) and they're both mothers.

The best match for a bone marrow transplant is when a patient and donor'shuman leukocyte antigen closely match. HLA"is a marker on our stem cells thatdetermines how our immune system responds," explained Hamdan. Those markers are used by an individual's immune system to know which cells belong in the body and which ones don't, according to Be The Match.

Doctors first looked to Torres' brother to see if he was a match. Siblings have a one in four chance of being a match since half of an individual's HLA markers are inheritedfrom their mother and the other halffrom their father, according to Be The Match. About seven out of 10 people won't have a close match with a family member, as was thecase with Torres. That's when people look to thedonor registry.

After Trinidad completed her cheek swab in October 2015, she essentially forgot about it since she didn't hear back from the registry. She received a phone call a year later.

"'Hey, I don't know if you remember you signed up for this, but this is what we do and we're calling to let you know that you have a possibility of saving someone's life,'" Trinidad recalled hearing.The only information she was given was the person needing the donationwas a female, 40 years old (Torres turned 40 in October 2016) and the type of leukemia. Nothing more, not even a name.

So, yes or no? It wastime to decide.

"I called them (the next day to learn) what did I need to do, what did they need from meto make sure it could be successful," she said.

Trinidad had blood work and other tests done prior to donation day. Her family was very supportive of her decision to help save a life, she said, whileit was a bit "hard for my friends to be on board."

"We were all 19, so they were like, 'You're crazy, you don't even know them and you're going to have this whole surgery for them?'I was like, "Well, yeah, I can save someone's life,'" Trinidad recalled. "You would want someone to do it for you, so how could you not do it?"

On donation day, donorsare put undergeneral anesthesia and marrow cells are taken from the back of the pelvicbone.

"The donor lies face down, and a large needle is put through the skin and into the back of the hip bone. Its pushed through the bone to the center and the thick, liquid marrow is pulled out through the needle," according to Cancer.org.Around 10%, or 2 pints, of marrow are collected, and the procedure takes up to two hours. The donor's body replaces those cells within four to six weeks.

Trinidad described the day in December 2016 as "nerve-racking,"but not because of the giant needle.

"I know everything that they're doing to me, but I can't, I literally cannot, know her perspective, what she is going through, how it is going to get to her," she said. "During this whole procedure, I'm nervous, I'm thinking, 'I hope it works, I hope it works.'I'm a match, but her body might not (accept the cells)well. I want to be sure that I'm doing the best I can so that it's the best for her."

To begin the transplant process, a receiving patient must undergo a conditioning regimen, which includes chemotherapy and sometimes radiation, to "wipe out" their immune system and leukemia cells, according to Hamdan.On transplant day, also called Day Zero, patients receive the donated cells through a blood transfusion.From Day Zero onward, the donated cells grow and make new blood cells, which is called engraftment, according to Be The Match.

Torres, admitted to the hospital on Thanksgiving, had a week straight of chemotherapy. Day Zero, which she considers one of her birthdays and her "rebirth," was Dec. 2, 2016.

It's normal for patients to feel weak, and Torres remembers being "sick to my stomach" the first few days after the transfusion. But her red and white blood counts started growing, she said, and slowly started feeling better. She was released from the hospital on Dec. 23, just in time for the holidays.

Both women had played a big part in each other's lives, and yet they still didn't know anything about one another.

Transplant recipients and donors have to wait one year before they can have direct contact with each other in the United States, according to Be The Match.

"This could only work if both of us want to know," Trinidad said."It was hard because I wanted to know her recovery, I wanted to know if it worked. What if it didn't work and they just didn't tell me anything at all?"

By the time the one-year mark came, the two women were ready to know something, anything,about each other.

It was an instant connection, almost as if they had known each other their entire lives, they both said. Finallyconnected on Facebook, they could get a glimpse of the other's family and see what they were up to. They talked and texted whenever they could.

It wasn't until a few weeks after their initial contact that Torres revealed to Trinidad that doctorsfound leukemia once again in January 2018.Torres would have to go through the transplant process all over again, but this time witha different donor.

Hamdan explained: "Transplants are most of the time the only chance for patients to be cured, and although there is a good chance of success, the cancer can come back. (It) depends on the disease, the age of the patient, the type of transplant."

Torres still wouldn't change a thing.

"She gave me life the first time around. I was able to come home and be with my kids for a year," Torres said. "Even if I had relapsed or not, Im so grateful for her for doing an act of kindness. At 20,Iwasnt thinking about stuff like that."

Trinidad, now a mother herself to3-month-old son Jimmy,said having her own child put thedonation into a whole new perspective.

"I really just am happy to give her that time with her kids. I now know how important and valued that time is," she said.

But thatwasn't the end of the journey.

They both had meeting each other in-person on their bucket lists, and when an opportunity came at aHOSA Future Health Professionals convention last month in Orlando, Floridaboth said "it was meant to be."

Representatives from Be The Match reached out to the two women and asked if they'd want to share their story to the students attending the conference. Trinidad was also a member of HOSA when she attended Palm Springs High School.

After years of texting, calling and social media lurking, they hugged on stage at the conference for quite a long time, admitted Trinidad, and "neither of us wanted to let go." She describedthe moment as "surreal,"finally seeing "the life that I gave her."

And for Torres, to see the woman who went froman anonymous lifesaver to a dear friend and a bit of a look-alike,saying thank you in-personis a moment she'll never forget.

"Theres no way that Iwill ever be able to repay her because theres no price with what she did," Torres said. "Im think I'm still kind of digesting all the emotions that came with it, but the one thing I know isIm full of gratitude for what she did for me.

Trinidad hopes more people will join the donor registry "it's so easy," she reiterated and be there to answer the call if they end up being someone's best match.

"I'm a donor because I wanted to be one," Trinidad said. "I know it required me physically giving up some bone marrow, but itsaved someones life, and I would do it again."

Torres, too, can attest to that: "If it hadnt been for her the first time around, honestly I dont think Iwould be here."

HOW TO JOIN THE BE THE MATCH REGISTRY

Visithttps://bethematch.org/to learnhow to join the registry, request a cheek swab and what the next steps are if you're a match.

Ema Sasic covers health in the Coachella Valley. Reach her at ema.sasic@desertsun.com or on Twitter @ema_sasic.

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Palm Desert resident meets the woman whose life she saved with bone marrow transplant - Desert Sun

Skin Stem Cells Comments Off on Palm Desert resident meets the woman whose life she saved with bone marrow transplant – Desert Sun | July 7th, 2021

A year before the pandemic, I was diagnosed with a condition called mast cell activation syndrome (MCAS). A hallmark of the syndrome is hypersensitivities in more than one organ system: Food and other triggers can give me abdominal pain and severe diarrhea; my nose swells and I sneeze and wheeze. That sounds like allergies, but I've never tested positive on an allergy test.

Mast cells are among the immune system's first line of defense. They are abundant in the parts of the body that have close contact with the outside world, including the skin, airways, and intestines. Mast cells gone wrong cause allergic symptoms, secreting histamine and giving us itchy eyes, hives, and rashes. Less well understood is their role in modulating the responses of other immune cells. Before the pandemic, researchers had suggested that mast cell dysfunction could explain severe cases of the flu and highlighted the cells' role in shutting down inflammation in a variety of situations. In my case, probably because of a genetic peculiarity, my mast cells overreact.

I was fairly stable on my medication, and then I became sick with Covid-19. Months after the virus had passed and I no longer had pneumonia, I was still fighting fatigue and breathlessness. My symptoms also flared up erratically. On some mornings, for example, the oatmeal I had relied on for years could cause me abdominal pain. "Once the mast cell response is turned up, it doesn't wind down just because the infection is gone," explained my doctor, Leo Galland, a New York internist who specializes in difficult cases.

MCAS often seems to first emerge after a virus. Could it explain any of the symptoms of the growing group of patients with long Covid? Congress has now dedicated more than a billion dollars towards research into why so many post-Covid patients roughly a quarter, more often women still feel ill long after their infection. In Facebook groups and elsewhere, people with plausible symptoms for instance, severe lingering rashes and months of hives have been trading information about remedies for the disease. Severe fatigue after exercise suggested myalgic encephalomyelitis/chronic fatigue syndrome, which some say is linked to MCAS. Others became lightheaded when they stood up, which might mean they had postural orthostatic tachycardia syndrome (POTS). Spend an hour searching online, and you'll find papers saying POTS, too, may be a manifestation of MCAS.

But getting a workup for the syndrome can be a long ordeal. The full range of tests and treatments aren't routinely covered by insurance, leaving some patients to pay thousands of dollars out of pocket. Before you get there, you need to find a sympathetic doctor: Researchers don't agree on whether the illness is rare, or quite common.

I was lucky; Galland took me on in the 1980s. Long before the microbiome became a news item, he diagnosed me with intestinal dysbiosis a disturbed gut. We don't know why I got sick when I did, but when I showed up in Galland's office, I was a young woman on an absurdly limited diet with a myriad of fluctuating symptoms. On a trip to Tucson, as just one example, my face and arms ballooned, and then shrank on the plane home. I had been exposed to a fungus in the desert. My grandmother commiserated; when her face swelled up, her doctors in Antwerp, in the 1930s, pulled out all of her teeth. She had no explanation.

Interestingly, disturbances in the gut may be linked to severe Covid-19, and correcting them a possible path to health for long Covid sufferers. Mast cells may have a unique role in communicating with gut bacteria. In midlife, I fit the profile for irritable bowel syndrome (IBS), the abdominal pain, often accompanied by diarrhea or constipation, that afflicts as much as 20 percent of the population, and often sets in after a virus. Desperate, in 2018, I had just completed a trial of hypnotherapy for IBS when my digestion took an embarrassing turn, with accidents in taxis, and I could no longer eat outside my home.

A new dietician, Tamara Duker Freuman, author of "The Bloated Belly Whisperer," helped me identify the worst offenders: foods that are high in histamine, which can be found in everything from alcohol to avocados. After further testing, Galland put me on a regime: an arsenal of mast cell modulators and anti-histamines, including Pepcid, which also blocks histamine.

And I got better.

* * *

Mast cells were first named in 1878 by a German-Jewish Nobel Prize winner, Paul Ehrlich, a father of modern immunology who is most famous for discovering the cure for syphilis. At the turn of the century, scientists discovered anaphylaxis, the classic mast cell allergic reaction. The word comes from the Greek ana (against) and phylaxis (protection). The idea that an immune response could actually hurt us, rather than protect us, came as shock. Current research about the gut and immunity may change the paradigm again.

Five decades later, in 1949, scientists described a rare genetic disorder called mastocytosis, in which mast cells produce clones, building up in the skin, bones, and other organs. It wasn't until the 1980s that researchers began to notice that mast cells could become hyper-responsive or over-activated without cloning.

On a separate track, since the 1990s, researchers have explored mast cell activity in IBS. (A clinical trial of Pepcid and Zyrtec for difficult IBS cases is currently underway at the University of Cincinnati.) Kyle Staller, director of the Gastrointestinal Motility Laboratory at Massachusetts General Hospital, now sometimes prescribes Pepcid if he sees other signs like hives, to patients who ask him to consider a histamine or MCAS issue. "I think anyone who's been following the science closely has to start wondering, 'How much could this be playing a role in that IBS patient who's in front of us on a given day?'" he told me.

Competing proposals for diagnostic criteria emerged after 2010. Both proposals say that doctors should rule out other explanations for a person's symptoms, and that symptoms should appear in a least two organ systems (in my case, it affects my gut, nose, and skin). Both proposals require lab tests but they disagree on which tests are necessary, and on the ranges that would indicate someone has MCAS, as well as other details. Because lab results are elusive, Galland and some other doctors rely on a medical history instead.

The disagreement has led to two camps. In camp one, the condition is rare; in camp two, it occurs in up to 17 percent of the adult population. Specialists in camp one say patients are misled: "More and more patients are informed that they may have [mast cell activation syndrome] without completing a thorough medical evaluation," an international group of 24 authors, led by Peter Valent, a hematologist and stem cell researcher at the Medical University of Vienna, wrote in April 2019 in the Journal of Allergy and Clinical Immunology.

A year later, a largely American group of 43 authors led by Lawrence Afrin, one of the earliest mast cell activation researchers, countered in the journal Diagnosis that patients are suffering and even dying from underdiagnosis. By then the pandemic had arrived, and Afrin suggested that some patients with long Covid might be experiencing MCAS.

Patients were seeing links as well. For example, the distinct POTS symptom of extreme lightheadedness, once often dismissed as a problem of anxious young women, emerged as one of the odder long Covid symptoms. POTS, which has been reported by patients who experienced Lyme and other infections, may involve histamine and several other chemicals released by mast cells. It is known to overlap with MCAS.

Last fall, when the Centers for Disease Control and Prevention reported on what it labeled multisystem inflammatory syndrome (MIS), the name rang bells: MCAS is clearly a multi-system inflammatory syndrome. Theoharis Theoharides, a professor of immunology at Tufts University who has studied mast cells for more than 40 years, wrote that MIS patients should be evaluated for MCAS.

Mariana Castells, director of the Mastocytosis Center at Brigham and Women's Hospital in Boston, told me in an email that she's seen no data showing that long Covid patients have the requisite diagnostic markers of MCAS.

Observers agree that the long Covid group probably includes people with different vulnerabilities. It would be marvelous indeed, if, one day, we found a single powerful concept to understand post-viral illness.

In the meantime, you might not need to fit either group's criteria for MCAS, a difficult and chronic illness, to experience your mast cells' betraying you sometimes. "Like many, many conditions, over time we [may] learn that there's a spectrum of disease," Staller said. "It's not an all or nothing phenomenon."

Even the group that sees MCAS as rare acknowledges the existence of a less severe form of mast cell activation that does not meet MCAS criteria. Theoharides has detailed several categories of the illness. He told me that he'd guess half of patients diagnosed with IBS might have mast cell activation of some kind.

If mast cell dysfunction is truly common, I trust the online buzz to help us find out. Crowdsourcing on patient forums is here to stay. And it's good, after all, that sick people shared information, found support, and made long Covid a "thing" with ontological status.

Growing up, I had wondered if my grandmother's multiple "allergies" were real. We didn't laugh, but we didn't exactly believe her. Then it happened to me.

* * *

Temma Ehrenfeld is a writer and ghostwriter in New York drawn to philosophy and psychiatry. Her most recent book is "Morgan: The Wizard of Kew Gardens."

This article was originally published on Undark. Read the original article.

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Immune system mutiny: mast cells and the mystery of long COVID - Salon

Skin Stem Cells Comments Off on Immune system mutiny: mast cells and the mystery of long COVID – Salon | July 7th, 2021

An immunotherapy based on supercharging the immune system's natural killer cells has been effective in treating patients with recurrent leukemia and other difficult to treat blood cancers. Now, researchers at Washington University School of Medicine in St. Louis have shown in preclinical studies conducted in mice and human cells that this type of cell-based immunotherapy also could be effective against solid tumors, starting with melanoma, a type of skin cancer that can be deadly if not caught early.

The study is published June 29 inClinical Cancer Research, a journal of the American Association for Cancer Research.

In recent years, an immunotherapy called immune checkpoint inhibitors has revolutionized treatment for advanced melanoma. In one well-known example, this immunotherapy was successfully used to treat former President Jimmy Carter, whose melanoma had spread to his liver and brain.

But the therapy only works in about half of such patients. And even among those who respond well to the initial therapy, about half go on to develop resistance to it. Consequently, researchers have been seeking different ways to harness the immune system to attack melanoma cells. One possibility is to use natural killer (NK) cells, a part of the immune system's first line of defense against dangerous cells, whether cancer cells or invading bacteria.

Todd A. Fehniger, MD, PhD, a professor of medicine, and his team have had success in clinical trials treating recurrent leukemia with a patient's own natural killer cells or those from a donor. The NK cells are harvested from the patient's or a donor's blood and exposed to a set of chemical signals called cytokines that activate the cells and prime them to remember this activation. When these "cytokine-induced memory-like" NK cells are given to the patient, they are more potent in attacking the cancer because they already have been revved up, as Fehniger puts it.

"These 'revved-up' memory-like NK cells attack blood cancers quite well," said Fehniger, the study's co-senior author and an oncologist who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "But relatively little work has been done on whether these cells can be used against solid tumors. This is an unmet need in solid tumor oncology. Our study provides proof of principle that memory-like NK cells respond better than normal NK cells against melanoma, and it serves as a stepping stone to a first-in-human clinical trial of these cells in advanced melanoma."

Added co-senior author Ryan C. Fields, MD, the Kim and Tim Eberlein Distinguished Professor of Surgical Oncology: "We hope this is also a step toward harnessing NK cells against multiple solid tumors. Melanoma was a good place to start because we know it responds to immune therapy. But because many patients don't respond or develop resistance, we felt that targeting a different aspect of the immune system was a promising strategy to pursue."

The standard checkpoint inhibitor immunotherapy that works well in some melanoma patients targets T cells, another type of immune cell that also frequently is harnessed against different forms of cancer. According to the researchers, patients who don't respond well or stop responding to the T cell-based standard therapy and have no other options would be good candidates for NK cell therapy.

The researchers studied human NK cells from both healthy people and from patients with melanoma and found that the cytokine-induced memory-like NK cells could effectively treat mice harboring human melanoma tumors. Tumors shrank to the point of being almost undetectable in many of the mice, and the memory-like NK cells prevented the tumors from returning in most cases for the duration of the 21-day experiment. While normal NK cells also reduced and controlled melanoma tumors, they did not do so to the same degree.

"We are currently designing a clinical trial to evaluate these NK cells in patients with advanced melanoma who have exhausted all other treatment options," Fehniger said. "We would like to investigate NK cells from a donor and, separately, a patient's own NK cells to see if the cytokine-induced memory-like NK cells offer an effective treatment option for patients with this aggressive skin cancer."

The NK cell-based immunotherapy is potentially safer than other cell-based immunotherapies because the NK cells do not trigger a cytokine storm, as is seen sometimes in CAR-T cell therapy, which often is used for blood cancers, nor do the NK cells cause graft-versus-host disease, which sometimes follows a stem cell transplant.

"Even 10 years ago, we had no effective therapies for advanced melanoma -- much like the lack of therapies for glioblastoma or advanced pancreatic cancer today," said Fields, a surgeon who treats patients at Siteman. "Checkpoint immunotherapy has revolutionized melanoma treatment, but we're still not satisfied with the 50% response rate. We want to do better, and this NK cell therapy is a promising approach. And in the future, we may be able to combine an NK cell-based therapy with checkpoint inhibition for an even better response."

Fehniger and his colleagues have worked with Washington University's Office of Technology Management to license the cytokine-induced memory-like NK cell technology to a company called Wugen. Fehniger is a co-founder of Wugen and serves on its scientific advisory board.

Reference:Marin ND, Krasnick BA, Becker-Hapak M, et al. Memory-like differentiation enhances NK cell responses to melanoma. Clin Cancer Res. 2021. doi: 10.1158/1078-0432.CCR-21-0851

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cell-Based Immunotherapy May Be Effective Against Melanoma - Technology Networks

Skin Stem Cells Comments Off on Cell-Based Immunotherapy May Be Effective Against Melanoma – Technology Networks | July 7th, 2021

The Body Shop discount codes are hard to come by, but when they *do* rear their beautiful heads (read: now - keeping scrolling), there's one product I always make a beeline for.

We're all well aware of the fact that we should be wearing face SPF every single day at this point. Stat. It's non-negotiable. Even when the weather is as grey and drizzly as it is this July. Sob. But which one? I've got a few on rotation - from Glossier's Invisible Shield to Ultra Violette's Queen Screen Luminising Sun Serum - though my most-reached for is The Body Shop's Skin Defence Multi-Protection Lotion SPF 50+ PA++++. It's really, really good.

A fan favourite for good reason, it's a 2-in-1 moisturiser and SPF 50+ product that helps to protect against pigmentation and premature ageing. On the hydration front, it has been newly formulated with red algae extract and vitamin C to help your skin look brighter and healthier. It's also super lightweight, fast-absorbing and non-greasy, so you don't feel like your face is caked in gloopy sun cream.

On the protection front, it has SPF50, so it effectively protects your skin against UV rays - including UVA, which penetrates deeper than any other kind of UV ray and causes pigmentation and discolouration. Plus, it serves up anti-pollution protection. Oh, and it leaves no white cast (tried and tested), so the coast is clear for dark skin sisters.

Buy It Now Claim Your Discount

Tempted? We don't blame you. And there's no time like the present to bag yourself a bottle. Not just because summer is hopefully upon us (we've heard whispers of 25 days of sunshine later this month!), but because you can get 15% off right now - taking it from 18 to 15.30. Dreamy. All you need to do is head to our The Body Shop discount codes page, and claim your discount. The promo code has no minimum order value attached, applies to both new and existing customers and is valid until further notice.

Elsewhere, you can get a free 250ml The Body Shop shower gel when you spend 25, free delivery at The Body Shop or 70% off in The Body Shop sale (think 10 body butters, 30% off gifts and *tonnes* of products for 15 and under).

Claim Your Discount

After more discount codes? Head this way for Cult Beauty discount codes, over here for LookFantastic discount codes and in this direction for Neom discount codes. We've also got Feel Unique discount codes, Selfridges discount codes and MAC discount codes.

For more from Glamour UK Commerce Writer Sophie Cockett, follow her on Instagram @sophiecockettx.

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The Body Shop Discount Codes: 15% Off Everything - GLAMOUR UK

Skin Stem Cells Comments Off on The Body Shop Discount Codes: 15% Off Everything – GLAMOUR UK | July 7th, 2021