CAR-T cell therapy remains viable for patients in lymphoma remission, study finds – News-Medical.Net

By Stem Cell Treatment

A study led by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine suggests that CAR-T immunotherapy remains a viable option for patients who have lymphoma that goes into remission before the cell therapy begins.

While the study doesn't answer the question of whether cell therapy in remission is the right choice, it does say that it's not the wrong choice.

"I don't think it answers the question of: Should we give these patients cell therapy? But I think it answers the question that we can that it's safe and that it's a reasonable strategy when you're in that spot," said Trent Wang, D.O., a Sylvester hematologist and cellular therapy specialist who will present study findings in an oral presentation at the 65th ASH Annual Meeting and Exposition, the American Society of Hematology's conference taking place in San Diego, California, Dec. 9-12.

Most patients receiving cell therapy, a form of immunotherapy that uses immune cells engineered to recognize and attack the patient's cancer, desperately need it. For some, it comes after many other treatments have failed. But Wang noticed an odd phenomenon in the past few years when treating lymphoma patients with this form of therapy: Some of his patients went into complete remission before the cells ever touched their bodies.

This uncommon scenario occurs during the process of getting to cell therapy, which in the case of Wang's study uses a kind of engineered immune cell known as CAR-T cells. When a patient starts the process, there's a waiting period of three to five weeks before they get the treatment. Insurance approval is needed, and the cells themselves need to be manufactured from the patient's own cells. But many of these patients are very sick with their cancer, so physicians will often treat them with a short course of chemotherapy or other drugs to tamp down the symptoms.

A small handful of these patients end up in remission during this waiting period treatment, the clinicians have found.

That prompted this dilemma: Now what are we supposed to do? Should we change the plan or give the therapy anyway? We just didn't have a lot of information on this scenario."

Trent Wang, D.O., a Sylvester hematologist

Wang said more often than not his team would proceed with the cell therapy in these cases, mainly to prevent yet another stretch of time where the patients' cancer might come back again. But it didn't feel like a very informed decision.

Wang and his colleagues noticed that their patients who received the cells while in remission tended to fare well after their infusion. But they didn't know if those results would hold up in an analysis of a larger group. They proposed a research study to the Center for International Blood & Marrow Transplant Research, a nationwide registry that tracks patients who have received transplants and/or cell therapies.

The study included data from 134 patients in the registry who had gone into complete remission in the waiting period before receiving their cell therapy. To find that group, the scientists screened the records for more than 5,000 cell therapy patients.

They found that this group of patients had a 43% probability of progression-free survival over the two years following their treatment, about the same percentage as patients in the registry who were not in remission when they received CAR-T. However, the patients in remission had very low levels of toxicities related to their cell therapies, namely an immune overreaction known as cytokine release syndrome and neurotoxicity, two side effects that can sometimes accompany CAR-T cell therapy.

The study used data from patients treated with CAR-T cell therapy between 2015 to 2021, and current frequencies of specific cell therapy use are slightly different from those that were used in practice just a few years ago, Wang said. Next, the researchers want to explore the data paralleling more recent treatment trends.

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Milestone Gene Therapies for Sickle Cell Disease Greenlit by FDA – Medpage Today

By Stem Cell Treatment

The FDA approved two cell-based gene therapies, exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia), for sickle cell disease (SCD), the agency announced.

Marking the first FDA-approved therapy utilizing CRISPR/Cas9 technology, Casgevy is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises (VOCs).

Lyfgenia, which uses a lentiviral vector for genetic modification, is approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events.

"These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health," said Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research (CBER), in a press release. "Today's actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA's commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health."

Casgevy is given to increase the production of fetal hemoglobin, which prevents the sickling of red blood cells.

With Lyfgenia, the patient's blood stem cells are genetically modified to produce a gene-therapy derived hemoglobin that functions similarly to hemoglobin A.

FDA approval for Casgevy was based on the pivotal clinical study CLIMB-121 in which 29 of 30 recipients achieved absence of severe VOCs for at least 12 consecutive months. The treatment has not been associated with excess severe adverse events.

Lyfgenia's approval was based on the phase I/II HGB-206 study that showed that 6-18 months post-treatment, 30 of 32 patients had severe vaso-occlusive events resolved, with 28 of them having no more vaso-occlusive events at all.

Of the 100,000 Americans with sickle cell disease, the roughly 20% who have more frequent vaso-occlusive crises -- namely, those in the hospital at least a few times a year -- are the ones who stand to benefit from these newly approved gene therapies, Marks clarified during a media briefing.

Both treatments are administered as one-time infusions. They are made from the patients' own blood stem cells, which are modified and returned to the patient in a hematopoietic stem cell transplant.

"Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today," said Nicole Verdun, MD, also at FDA's CBER, in a statement.

"Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited," Verdun continued.

Unlike the CRISPR/Cas9 product, Lyfgenia carries a black box warning on its label about hematologic malignancy due to the death of two trial participants who developed acute myeloid leukemia, Verdun said during the briefing.

Whether there is an excess malignancy risk unique to Lyfgenia remains unclear without more follow-up. Verdun said the drug sponsors have agreed to long-term follow-up of 15 years plus lifetime monitoring for malignancy.

Marks stressed that the totality of all side effects that patients may encounter -- from the gene therapies themselves, their conditioning regimens, or additional care to get people off their current medications -- will have to be considered.

Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

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FDA approves CRISPRCas9 therapy for sickle cell disease – ASBMB Today

By Stem Cell Treatment

Officials at the U.S. Food and Drug Administration todayannouncedapproval ofthe first CRISPRCas9 therapeutic to treat sickle cell disease. The cell therapy is the only cure to date for patients who are not eligible for stem cell transplants. The FDA approved the therapy for patients age 12 to 35.

Casgevy uses CRISPRCas9 technology to edit a patients own hematopoietic stem cells to produce high levels of fetal hemoglobin, which is not normally expressed at adulthood and drowns out the damaging effects of sickle hemoglobin.

The therapeutic, exagamglogene autotemcel, sold as Casgevy, from CRISPR Therapeutics and Vertex Pharmaceuticals, uses CRISPRCas9 technology to edit a patients own hematopoietic stem cells to produce high levels of fetal hemoglobin, which is not normally expressed in adulthood and drowns out the damaging effects of their sickle hemoglobin. The therapy was approved in the United Kingdom in November.

Sickle cell disease is a debilitating, genetic disorder that causes abnormal red blood cell development. It affects approximately 7.74 million individuals worldwide. Red blood cells are normally disk-shaped and move easily throughout the blood, carrying oxygen to vital organs. In a patient with sickle cell disease, red blood cells are warped, or sickle-shaped, which can lead to impaired blood flow and cause stroke, infection, eye issues, severe pain crises and premature death.

The therapeutic specifically targets BCL11A, a repressor of the fetal hemoglobin gene, using a guide RNA. The precise target site is a residue within the BCL11A enhancer region, which, once modified by the Cas9 nuclease, takes the brakes off the fetal hemoglobin gene, leaving transcription and later translation free to occur.

Victoria Gray, a mother of four from Mississippi, was the first sickle cell patient to receive Casgevy in a 2019 clinical trial. Prior to the treatment, Gray said she had to rush to the emergency room at least once a month and often stay in the hospital for weeks at a time due to her painful crises. Since receiving Casgevy, she has had no emergency room visits, hospital stays or crises, she said.

I feel cured, Gray said. My life has changed dramatically with just a leap of faith.

Emmanuelle Charpentier is a biochemist, microbiologist and geneticist, recognized as an expert in regulatory mechanisms underlying processes of infection and immunity in bacterial pathogens.

Emmanuelle Charpentier is a cofounder of CRISPR Therapeutics and the director of and a scientific member at the Max Planck Unit for the Science of Pathogens. Charpentier shared the 2020 Nobel Prize in chemistry for the development of CRISPRCas9 with Jennifer Doudna, an RNA biochemist at the University of California, Berkeley.

Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, commented on today's action.These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health, Marks said. Todays actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDAs commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.

The FDA approved Casgevy based on three studies showing that the drug is a safe and effective treatment for sickle cell disease. In the most recent safety and efficacy clinical trial, patients like Gray who received the therapeutic sustained long-term high levels of total hemoglobin, similar to what is seen in healthy adults, and most were blood transfusionindependent and free of painful crises for at least one year after treatment.

Benjamin Oakes, CEO and cofounder of Scribe Therapeutics, said The approval is just the tip of the iceberg. It's a really beautiful proof of concept for what CRISPR genome editing can do. The real vision and mission for the whole CRISPR field should be to create safer, more effective therapies that can be brought more broadly to patients.

Benjamin Oakes is cofounder and CEOof Scribe Therapeutics.

Oakes said he and his colleagues are developing the next generation of CRISPR gene therapies using an engineered CasX protein that cuts DNA more precisely than Cas9.

According to the Institute for Clinical and Economic Review, Casgevy could be priced at up to $1.93 million to be cost-effective, a measure that estimates how much it costs to gain a unit of a health outcome, such as a life year gained or a death prevented. With this price tag, ICER estimated that 15% of eligible patients could be treated over a five-year period.

In 2022, patients with sickle cell disease incurred out-of-pocket medical costs totaling up to $44,000, with insurers covering approximately $1.7 million per patient. Economists predict that gene therapies like Casgevy could cost a single state Medicare program more than$30 million per year.

The FDA will evaluate a second gene therapy for sickle cell disease, bluebird bios lovo-cel, later this month. Unlike Casgevy, lovo-cel uses a lentiviral vector to introduce a modified beta globin gene into patient stem cells. This modified gene produces an antisickling hemoglobin protein, which is designed to inhibit the polymerization of mutant sickle hemoglobin, making it less likely to form blockages in the circulation.

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FDA Approves A CRISPR-Based Therapy for Sickle Cell Disease – geneonline

By Stem Cell Treatment

FDA Approves A CRISPR-Based Therapy for Sickle Cell Disease

After CASGEVY (exagamglogene autotemcel) passed the U.S. Food and Drug Administrations (FDA) Biologics License Application (BLA) in June this year (2023), Vertex Pharmaceuticals and CRISPR Therapeutics announced its FDA approval on December 8. CASGEVY is the first FDA-approved treatment utilizing the novel genome-editing technology CRISPR, marking an innovative advance in gene therapy and offering a glimmer of hope for patients with severe sickle cell disease (SCD). Approximately 16,000 patients aged 12 years and older with recurrent Vaso-Occlusive Crisis (VOC) are now eligible to receive this innovative one-time treatment.

Related article: Vertex and CRISPR Collaborate Again with $330 Million Diabetes Gene Editing Deal

The administration of CASGEVY requires specialized knowledge in stem cell transplantation. Vertex is actively collaborating with proficient hospitals to establish Authorized Treatment Centers (ATCs) throughout the United States. Notable institutions involved in this initiative include Boston Medical Center, Childrens National Hospital, and City of Hope Childrens Cancer Center, among others. These ATCs are set to play a pivotal role in facilitating the delivery of CASGEVY to eligible patients. The companies have outlined plans to introduce additional ATCs in the forthcoming weeks, expanding accessibility for patients in need.

CASGEVY, a genome-editing cell therapy, leverages CRISPR/Cas9 technology to edit autologous CD34+ hematopoietic stem cells. This targeted approach aims to diminish BCL11A expression, leading to an increased production of fetal hemoglobin (HbF). Through the reduction or elimination of vaso-occlusive crises, CASGEVY holds the promise of significantly enhancing the quality of life for individuals affected by sickle cell disease (SCD). The therapy has obtained conditional marketing authorization in the United Kingdom and Bahrain. Regulatory agencies in Europe and Saudi Arabia are actively reviewing CASGEVY, with ongoing assessments for its investigational use in treating transfusion-dependent thalassemia (TDT).

The approval marks a significant milestone, not just in the landscape of sickle cell disease (SCD) treatments but also in advancing the frontier of CRISPR-based therapies. The success of CASGEVY represents a noteworthy leap forward in the realm of genetic medicine, offering hope and potential therapeutic avenues for those who require them.

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Modified Stem Cell Transplant Procedure Shows Favorable Results in Adults Living with Severe Sickle Cell Disease – InvestorsObserver

By Stem Cell Treatment

Less Toxic Approach to Haploidentical Bone Marrow Transplantation in Adults Living with Severe Sickle Cell Disease Offers Promise

LBA-4 : Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN

SAN DIEGO , Dec. 12, 2023 /PRNewswire/ --Stem cell transplantation is a potentially curative treatment for sickle cell disease (SCD), but it is not feasible for most people, often due to a lack of suitable donors or the inability to tolerate the intensive chemotherapy required as part of the treatment. In a new study, presented during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, adults living with severe SCD saw good outcomes from a modified transplantation procedure that broadens the potential donor pool and includes a gentler conditioning regimen, suggesting a less toxic approach could allow a much broader array of people to benefit from the treatment.

"This is a pragmatic approach for adults with SCD, and the results are fantastic," said Adetola A. Kassim , MBBS, MS , professor of medicine at Vanderbilt University Medical Center, the study's lead author. "It actually beat our expectations. This study has clearly shown that you can take selected adult patients with significant comorbidities to transplant, and hopefully change the trajectory of their disease."

The trial is the largest multi-center study to date to test the modified approach in adults with SCD.

SCD is an inherited blood disorder in which red blood cells become misshapen, diminishing their ability to carry oxygen. It causes episodes of severe pain, called vaso-occlusive crises, as well as damage to tissues and organs that accrue over time and can lead to early death. A stem cell transplant can cure the disease by removing the stem cells that produce misshapen blood cells and replacing them with stem cells from a donor that will make healthy blood cells.

The standard transplantation procedure for SCD requires that the donor be a sibling with a high degree of genetic similarity and that the recipient be healthy enough to tolerate a high-intensity chemotherapy regimen as part of the procedure. In the modified procedure used for the study, called related, reduced intensity haploidentical bone marrow transplantation, the donor only needs to be "half-matched" genetically to the recipient, broadening the pool of potential donors to include not only siblings but parents, children, cousins, aunts, and uncles.

While fewer than one-quarter of people with SCD have a matched sibling who could potentially serve as a donor, about 90% have a relative who could serve as a half-matched donor. In addition, because it uses a lower intensity conditioning regimen, the modified approach is more easily tolerated by people with health problems such as organ damage, a complication of SCD that becomes more common with age.

As a result of these modifications, a much broader group of people living with SCD could be eligible for reduced intensity haploidentical bone marrow transplantation than for conventional matched-donor transplantation, including older individuals, those with more comorbidities, and those without a matched sibling donor.

For the study, researchers enrolled 54 individuals living with SCD with a history of stroke or reduced heart functioning, pain episodes, or frequent blood transfusions. Forty-two participants ultimately underwent the modified stem cell transplantation procedure. At two years, the overall rate of survival following the transplant was 95% and the estimated rate of event-free survival (defined as survival without graft failure or a second infusion of stem cells) was 88%.

At 100 days following the transplant, 4.8% of patients experienced a primary graft failure and 4.8% experienced adverse events of grade three or higher. Infections were common; 78.6% of patients experienced at least one hospital admission following their transplant, most due to infections. Two participants died within the first year after the transplant, one from organ failure and one from fluid buildup in the lungs associated with COVID-19 infection.

Most participants experienced significant improvements in markers of healthy blood functioning, a reduction in pain episodes and fatigue, and improved heart and lung functioning. Overall, researchers said that the results suggest the modified procedure can achieve results that are comparable to conventional stem cell transplantation and is tolerable even for people with health conditions that would make them ineligible for a conventional transplant.

In future studies, the researchers plan to focus on opportunities to reduce rates of infection, enhance supportive care, and preserve fertility among people undergoing the procedure. They also plan to continue to follow trial participants to track long-term outcomes.

"Some of these patients are really thriving and now getting back into the community," said Dr. Kassim. "Our hope is that long-term follow-up will be able to quantify the added value of curing patients of SCD." Dr. Kassim added that most patients were off immunosuppression therapy at both the one and two-year post-transplant timepoints with no significant chronic graft-versus-host disease, providing evidence that the study's cyclophosphamide-based post-transplant regimen helped to reduce the risk of this serious complication.

Researchers noted that for many people, the feasibility of this treatment will depend not only on the availability of family donors, but on costs and insurance coverage, the ability to take time off work and even temporarily relocate to undergo the procedure, and the availability of family and caregiver support.

This study was funded by the National Heart, Lung and Blood Institute and the National Cancer Institute.

Adetola Kassim , MBBS, MS, of Vanderbilt University , will discuss this study in the Late-Breaking Abstracts Session on Tuesday, Dec. 12, 2023 , at 9:00 a.m. Pacific time in Hall A ( San Diego Convention Center).

###

The American Society of Hematology (ASH) ( hematology.org ) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology.

ASH's flagship journal, Blood ( bloodjournal.org ) is the most cited peer-reviewed publication in the field, and Blood Advances ( bloodadvances.org ) is an open-access, online journal that publishes more peer-reviewed hematology research than any other academic journal worldwide. Two new journals will be joining the Blood Journals portfolio in 2024, Blood Neoplasia ( bloodneoplasia.org ) and Blood Vessels, Thrombosis & Hemostasis ( bloodvth.org ).

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Stem cell therapy trial shows promise for regenerative treatment of heart failure – News-Medical.Net

By Stem Cell Medicine

Stem cell-based therapy improved quality of life for patients with advanced heart failure, Mayo Clinic researchers and international collaborators discovered in a late-stage multinational clinical trial. In one of the largest studies of cell intervention after a heart attack, patients reported their daily hardship lessened when stem cells optimized for heart repair supplemented standard of care. This clinical study further documented lower death and hospitalization rates among those treated with cell therapy. This research is published in Stem Cells Translational Medicine.

"In this era of global aging, people live longer, yet are at risk of chronic disease imposing a poor quality of life. Heart failure is an emerging epidemic in need of new healing options," says Andre Terzic, M.D., Ph.D., a Mayo Clinic cardiovascular researcher and lead author on the paper. "The stem cell-based approach in the present study demonstrates sustained benefit on physical and emotional health in response to biotherapy."

Dr. Terzic is the Marriott Family Director, Comprehensive Cardiac Regenerative Medicine for the Center for Regenerative Biotherapeutics.

Approximately 800,000 people in the U.S. suffer heart attacks every year. Damage to cardiac muscle weakens the heart's ability to pump blood through the body, leading to heart failure -; a debilitating and life-threatening disease. People with heart failure often suffer a diminished quality of life associated with shortness of breath, fatigue, swollen legs and limited daily activities. Standard of care for heart failure includes a heart-healthy diet and habits, medications, implantable devices, and rehabilitation. However, current regimens do not work for everyone, especially in advanced disease stages.

The study team recruited 315 patients from 39 hospitals in 10 countries who had advanced heart failure despite receiving standard of care. Patients were randomly divided into groups that would receive stem cell therapy versus those who would not. Patients assigned to cell treatment underwent cardiac catheterization. Then, stem cells taken from their own bone marrow and programmed to heal damaged heart tissue were delivered to the heart. Patients assigned not to receive stem cells had cardiac catheterization without cell delivery -; known as the sham treatment.

All participants were asked to complete a 21-question self-assessment at the beginning of the study and then again at 26-, 39- and 52-weeks following treatment. For each question, they rated their physical, behavioral and emotional states on a scale of 0 to 5.

During the one-year follow-up, patients with preexisting left cardiac chamber enlargement consistently reported improved quality of life after cell therapy over those who received the sham treatment. In parallel, lower death and hospitalization rates were recorded among those who received stem cells.

Data from one of the largest cardiovascular cell therapy trials, testing a regenerative technology discovered at Mayo Clinic, indicate benefit in both quantity and quality of life in advanced heart disease. The benefit of regenerative care has been typically evaluated on the basis of clinician-reported outcomes. What's unique in this study is that it was designed to listen to the patient's experience."

Satsuki Yamada, M.D., Ph.D., Mayo Clinic cardiovascular researcher and first author on the study

This clinical trial was conducted in a double-blinded fashion, with both participants and their healthcare professionals masked during the study assignment. A double-blind study is designed to reduce the risk of bias when evaluating patient outcomes.

Further independent clinical studies are needed to validate the findings of this research.

Marriott Family Foundation and National Institutes of Health (R01 HL 134664) provided funding. The Mayo Clinic Van Cleve Regenerative Medicine Program, Gerstner Family Foundation, Tanoto Foundation, and Mayo Clinic Center for Regenerative Biotherapeutics provided additional support.

Source:

Journal reference:

Yamada, S., et al. (2023). Cell Therapy Improves Quality-of-Life in Heart Failure: Outcomes From a Phase III Clinical Trial. Stem Cells Translational Medicine. doi.org/10.1093/stcltm/szad078.

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Companies Market Stem Cell Treatments to Long COVID Patients – Medpage Today

By Stem Cell Medicine

Clinics that sell stem cell and exosome treatments have turned their attention to long COVID patients, researchers found.

Among 38 businesses selling such treatments for COVID-19, the majority (36) marketed those therapies for long COVID, stated Leigh Turner, PhD, of the University of California Irvine, and colleagues in Stem Cell Reports.

"We didn't think the pattern was going to emerge as strongly as it did," Turner told MedPage Today.

Turner and his team have tracked stem cell clinics for years, building a database of clinics that operate in this arena. When the COVID-19 pandemic hit, they logged how these businesses were taking advantage of patients' fears by selling purported treatments for COVID.

They revisited some of those businesses last fall to see whether anything had changed as the pandemic shifted -- and lo and behold, it had.

"The pandemic has changed over time, and now there's a whole population of individuals who have had COVID-19, and they haven't completely recovered," Turner said. "They have lingering symptoms that are sometimes quite serious, sometimes life-altering" -- and that can make people desperate to find treatments, he added.

"We have a population of patients who are looking for symptomatic relief," Turner continued. "While we have long COVID clinics, people may not have an easy time getting access to them. There are long waits. And the interventions themselves may be rather limited in their effects."

That has left the door wide open for stem cell marketers to try to reach these people, Turner said.

For their study, the researchers used three strategies to find stem cell and exosome clinics marketing to COVID patients online. They looked at an earlier database of 1,480 stem cell or exosome businesses in the U.S., searched Google for additional companies both in the U.S. and abroad, and looked at businesses mentioned in Turner's 2021 Cell Stem Cell paper on companies selling stem cell treatments for COVID.

They revisited and re-analyzed all company websites in September 2022, with a final fact-check in October 2022.

Overall, they found 38 businesses that were advertising stem cell and exosome treatments for COVID, which were connected to 60 clinics.

Most of them were specifically marketing these therapies to patients with long COVID, while six businesses marketed their therapies as "immune boosters," five claimed to treat acute COVID infection, and two claimed their products could prevent COVID.

The vast majority of these businesses were based in the U.S. (40%) and Mexico (37%), while four were in Ukraine, two were in the Cayman Islands, and other countries appeared to have one business each: Guatemala, Malaysia, Panama, Philippines, Poland, Spain, Thailand, and the United Arab Emirates.

Turner and colleagues found that these products weren't cheap. Among the nine businesses that provided information on how much they charged, the least expensive product was $2,950, while the most expensive product cost $25,000. The average listed cost was $11,322, they found.

Turner said there are "plenty of things that can go wrong" when it comes to purported stem cell treatments for long COVID. These treatments are investigational and don't have scientific evidence behind them proving their success for the condition, he said.

A patient's "situation can be made dramatically worse if they're given an infusion of a product that hasn't been carefully studied or tested," Turner told MedPage Today. "There's a real possibility for serious injury in that situation, whether it's pulmonary embolism, an infection, or something else."

Indeed, many examples of stem cell treatments causing infections and other problems have been reported. The hit podcast "Bad Batch" examined an instance in which 12 people were hospitalized after getting contaminated stem cell injections. Nebraska health officials reported an outbreak of severe infections after exosome therapies. And researchers reported on three patients who had severe vision loss after intravitreal injections of autologous adipose tissue-derived stem cells.

There's also "an obvious possibility for financial scams," Turner said. "At an average price of $11,000, it's not like going to the store and buying some dietary supplements."

Turner said regulators should get tougher on companies peddling stem cell and exosome treatments for long COVID.

"I think it's a modest number," he said, referring to the 36 businesses his team discovered. "This seems like activity that probably deserves to be prioritized and seems like the kind of challenge the FDA and FTC [Federal Trade Commission] could actually do something about in a comprehensive way."

The FDA and FTC have pursued stem cell companies in the past, with both regulators issuing warning letters to such companies. One healthcare professional was even sentenced to jail time for selling a fake stem cell therapy.

Still, many businesses have avoided attracting regulators' attention, Turner said: "There's a lot the FDA has done, but there's still a massive marketplace."

The study was limited because it likely identified only some companies operating in this space. Also, the researchers searched only in English, and searches in other languages may reveal additional companies. In addition, businesses may have used other forms of advertising -- including billboards, newspaper or magazine ads, and radio or TV commercials -- to reach their potential customers.

"It is understandable that individuals seeking relief from shortness of breath, fatigue, 'brain fog,' heart palpitations, loss of smell, and other symptoms search for interventions that might help them," Turner and colleagues wrote. "Acknowledging the suffering and agency of such persons, members of this patient population are vulnerable to having their suffering, desperation, and hope exploited by entities making appealing therapeutic claims without having the scientific evidence needed to make such representations."

Kristina Fiore leads MedPages enterprise & investigative reporting team. Shes been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow

Disclosures

The project is supported by the Pew Charitable Trusts.

Turner disclosed serving as an expert witness in cases regarding unapproved stem cell treatments, as well as relationships with the International Society for Stem Cell Research and the International Society for Cell and Gene Therapy.

Primary Source

Stem Cell Reports

Source Reference: Turner L, et al "Businesses marketing purported stem cell treatments and exosome therapies for COVID-19: An analysis of direct-to-consumer online advertising claims" Stem Cell Rep 2023; DOI: 10.1016/j.stemcr.2023.09.015.

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Stem cell study reveals how infantile cystinosis causes kidney failure and how to cure it – EurekAlert

By Stem Cell Medicine

image:

This image, produced by a fluorescence microscope,shows a normal renal proximal tubule, the specific nephron segment in the kidney that is impaired in the rare disease infantile cystinosis. The red, green and yellow regions indicate the presence of different proteins in the tubule and the blue indicates the presence of nuclei. The UB researchers generated the tubule in the image from stem cells derived from an individual who does not have the disease.

Credit: Alexandra Kojac

BUFFALO, N.Y. University at Buffalo research has identified how a misstep in the genesis of a key component of the kidney causes infantile cystinosis, a rare disease that significantly shortens the lifespan of patients. Published Nov. 30 in theInternational Journal of Molecular Sciences, the work reveals that the mechanisms that cause the disease could be addressed and potentially cured through the genome-editing technique CRISPR. That could make kidney transplants, the most effective treatment currently available for these patients, unnecessary.

Infantile cystinosis, the most common and most severe type of cystinosis, occurs as the result of an accumulation in the bodys cells of cystine, an amino acid. The buildup damages cells throughout the body, especially the kidneys and the eyes. Treatment consists of medications that work to lower the level of cystine in the body, as well as therapies that address the impaired growth of these children due to the inability to properly absorb nutrients. Some children require feeding tubes. Eventually, patients with infantile cystinosis, also called nephropathic cystinosis, will require dialysis and a kidney transplant.

Promise of stem cells

Human-induced pluripotent stem cells (hiPSCs) are stem cells that can differentiate into many different cell types. They hold tremendous potential for studying genetic diseases; the drawback has been that differentiation into certain cell types has been problematic. Such is the case with many cell types found in the kidney.

But a new protocol developed by this research team was successful.

When our normal human-induced pluripotent stem cells were subjected to the differentiation protocol we developed, we were able to demonstrate extensive expression of physiologically important markers of the renal proximal tubule, the specific nephron segment that is altered in this disease, saysMary L. Taub, PhD, senior author on the paper and professor of biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB.

Ramkumar Thiyagarajan, PhD, assistant professor of geriatric studies at the University of Kansas and formerly a postdoctoral fellow at UB, is first author on the paper.

The protocol involved extracting stem cells from a healthy individual and an individual with infantile cystinosis. The researchers developed a culture medium to grow stem cells that included a small number of defined components present in blood, including insulin, specific proteins, growth factors and others. Conducting the differentiation protocol under these conditions occurred in a timely manner, says Taub, we didnt have to wait for weeks on end, and it occurred in a reproducible manner.

The researchers were able to efficiently differentiate the hiPSCs into the kidney proximal tubule, the type of nephron in the kidney that is impaired in infantile cystinosis, as well as in other kidney diseases.

Unlike in other studies, we were able to retain a number of markers in the tubule that are physiologically important in the kidneys reabsorptive functions, says Taub. Although these markers were expressed in both the normal and the cystinosis-derived hiPSCs, the genesis of the tubule was impaired in the cystinosis-derived cells, mimicking what happens in infantile cystinosis.

A potential cure

That finding means that the CRISPR genome-editing technique could be used to repair the defective genome and potentially cure the disease. The normal gene can be introduced in the genome of cystinotic hiPSCs, which can then be injected in the kidney to replace the defective proximal tubules of individuals with infantile cystinosis, Taub says.

In cystinotic individuals, it is the renal proximal tubule that degenerates, presumably due to programmed cell death, explains Taub, so the entire kidney would not need to be replaced. The defective renal proximal tubules of individuals with this disease can be replaced with normal tubules following the introduction of the normal gene into cystinotic hiPSCs obtained from the patient. And because these tubules are from cells derived from the patient, there should be no problem with tissue rejection.

The findings are applicable to other kidney diseases where the renal proximal tubule is damaged, including acute kidney injury that can lead to chronic kidney disease and renal failure, and can be fatal.

Initial studies will need to be conducted with animal models as well as with in vitro tissue culture cells.

The research was funded byUBs WNYSTEM and The Cystinosis Research Foundation.

International Journal of Molecular Sciences

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Stem cell study reveals how infantile cystinosis causes kidney failure and how to cure it - EurekAlert

Orca-Q Demonstrates Early Efficacy, Tolerable Safety in Haploidentical Stem Cell Transplant Without PTCy – Targeted Oncology

By Stem Cell Medicine

Bone marrow: 7activestudio - stock.adobe.com

The high-precision cellular product Orca-Q showcased early signals of clinical activity and an acceptable safety profile in patients receiving a haploidentical stem cell transplantation (haplo-SCT) without posttransplant cyclophosphamide (PTCy), according to findings from a phase 1 trial (NCT03802695) presented during the 2023 ASH Annual Meeting.1

Results showed that both the graft-vs-host disease (GVHD) relapse-free survival (GRFS) rate and overall survival (OS) rate at 1 year was 82% (95% CI, 65%-94%) with Orca-Q. This is in comparison to historical data with conventional PTCy for haplo-SCT, with recent 1-year GRFS rates of 46%.

These findings show promising safety and efficacy outcomes using Orca-Q cell therapy for haploidentical transplant, said Samer A. Srour, MB ChB, MS, lead study author and assistant professor in the Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, in an oral presentation during the meeting. No safety signals in this haploidentical setting were identified.

Standard allogeneic SCT can be a curative approach for patients across many high-risk hematologic cancers, although access to this therapy was previously limited to those who have a fully matched donor. The introduction of PTCy as prophylaxis for GVHD increased the utility of haploidentical donors; however, it has also increased relapse rates and toxicity issues such as cytokine release syndrome (CRS), delayed engraftment and T-cell reconstitution, mucositis, infections, cardiac events, and non-relapse mortality, Srour added.

However, GRFS rates in this patient population remain low. Through allograft optimization, Orca-Q improves haplo-SCT with its fully defined stem and immune cells, which consist of hematopoietic stem and progenitor cells, invariant natural killer cells, regulatory T cells, and CD4+/CD8+ T-cell subsets.

Orca-Q is derived from granulocyte colony stimulating factor that is mobilized during peripheral blood apheresis and is manufactured centrally at a Current Good Manufacturing Practice Manufacturing Facility in Sacramento, California. Its administration involves a vein-to-vein time of less than 72 hours across the United States, Srour noted, adding that the vein-to-vein time was within 60 hours for most cases on the study.

The multicenter, dose-expansion trial enrolled patients aged 18 to 65 years with the following high-risk hematologic cancers: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), very high or high-risk myelodysplastic syndrome, or myelofibrosis. Patients were required to be undergoing a haplo-SCT with negative donor-specific antibodies and were eligible for myeloablative chemotherapy with a Hematopoietic Cell Transplantation-specific Comorbidity Index 4 or lower, a Karnofsky performance score of at least 70, and adequate organ function.

Orca-Qs regimen begins with myeloablative conditioning on days -10 to -2, followed only by single-agent tacrolimus on day -1no PTCy or additional immunosuppressive therapies are administered. A fresh Orca-Q infusion is given on day 0, and tacrolimus is tapered on day +60 (posttransplant).

The studys primary end points are dose-limiting toxicities and primary graft failure.

Off the 33 patients enrolled onto the study, the median age is 43 years (range, 21-63) and 27% of patients were female; a total 30.3% of patients identified as Hispanic or Latino. Patients were Asian (15.2%), Black or African American (21.2%), White (42.4%), or other (21.2%). Their primary disease was ALL (30.3%), AML (63.3%), or chronic myeloid leukemia (6.1%). Additionally, patients had high-/very highrisk disease (18%), intermediate-risk disease (79%). Disease risk index was not applicable for 3% of patients.

Patients disease status at time of transplant encompassed those who achieved their first complete remission (CR1; 73%), second CR (CR2; 24%) and CML accel phase (3%). Patients either had a total body irradiation (TBI)-based conditioning regimen (51.5%) or busulfan-based one (48.5%). Donor characteristics showed that there were more male donors (73%) vs female donors (27%), and the CMV status was positive (30.3%), negative/not detected (36.3%), or not available (33.3%).

Rapid engraftment with Orca-Q was observed in the patients. The median engraftment time with neutrophils was 12.0 days (range, 8-25) and 15.5 days with platelets (range, 8-79). Two patients experienced secondary graft failure, and grade 1/2 CRS occurred in 3 patients (grade 1, n = 2; grade 2, n = 1).

Additional data showed a low incidence of severe Common Terminology Criteria for Adverse Events grade 2 (CTCAE; n = 9) and CTCAE grade 3 (n = 15) infections. There were 5 events (15%) of acute grade 2 to 4 GVHD and 1 event of grade 3 acute GVHD. At a median follow-up of 375 days (range, 73-1384), no patients have developed moderate to severe chronic GVHD. This in comparison to historical cohorts with PTCy, which show 1-year chronic GVHD rates of 24% to 33%.2

The phase 1 trial is continuing to enroll patients across the United States. Srour stated that there are plans to increase the age criteria to 75 years and provide less-intensive conditioning therapy.

Editors Note: Dr Srour disclosed research funding from Orca Bio for this study.

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Orca-Q Demonstrates Early Efficacy, Tolerable Safety in Haploidentical Stem Cell Transplant Without PTCy - Targeted Oncology

Stem Cell-Based Therapy: A Ray of Hope for Advanced Heart Failure Patients – Medriva

By Stem Cell Medicine

In a groundbreaking multinational clinical trial led by Mayo Clinic researchers and international collaborators, it was discovered that stem cell-based therapy significantly improved the quality of life for patients suffering from advanced heart failure. The study, one of the largest of its kind, involved 315 patients from 10 countries and revealed lower death and hospitalization rates among those treated with cell therapy. The research, funded by the Marriott Family Foundation and National Institutes of Health, was published in Stem Cells Translational Medicine.

The study demonstrated that patients who received stem cell therapy experienced a lessened daily hardship and a sustained benefit on both physical and emotional health. This promising form of biotherapy involves extracting stem cells from the patients own bone marrow and programming them to heal damaged heart tissue.

This trial stands out in the field of regenerative medicine, showcasing the potential of stem cell-based therapy in improving the quality of life for patients with advanced heart failure. The reduced daily hardship reported by patients, as well as the lower death and hospitalization rates, indicate the effectiveness of this therapy. Moreover, the sustained benefits on physical and emotional health emphasize the potential of biotherapy in the management of advanced heart disease.

The clinical trial was conducted in a double-blinded fashion, involving 315 patients from 39 hospitals across 10 countries. The results showed a significant improvement in the patients who received stem cell therapy, with lower death and hospitalization rates. The research was one of the largest studies of cell intervention after a heart attack, and patients reported a lessening of their daily hardship when stem cells optimized for heart repair were added to the standard of care.

The Mayo Clinic has long been at the forefront of regenerative medicine, seeking to harness the power of cells, tissue, and genes to provide first-of-their-kind therapeutics for patients in early-stage clinical trials. In other studies, Mayo Clinic researchers have demonstrated a nearly 20% increase in human papillomavirus (HPV) vaccination rates among adolescents through a combination intervention approach.

While the results of this clinical trial are promising, further independent clinical studies are needed to validate the findings and better understand the potential of stem cell-based therapy in treating advanced heart failure. As advancements in this field continue to emerge, the hope for patients suffering from heart diseases grows stronger.

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Stem Cell-Based Therapy: A Ray of Hope for Advanced Heart Failure Patients - Medriva