Category Archives: Cell Medicine

Researchers at University of California San Diego have found that the most common form of liver cancer one with a high mortality rate can be better targeted and treated using an innovative new stem cell-derived therapy, according to a recently published study in Cell Stem Cell.

The treatment, not yet studied in patients, involves the lab engineering of natural killer (NK) cells white blood cells that destroy tumor cells to more effectively battle hepatocellular carcinoma (HCC), one of the most treatment-resistant types of solid tumor.

Genetically modified NK-cell therapy doesn't require personalization like chimeric antigen receptor (CAR)-expressing T-cell therapy a relatively new, personalized form of immunotherapy. That means an NK-cell therapy could be mass produced and shelf-ready for patients, who could begin therapy without delay, their new research shows.

To some extent all tumor cells perhaps hepatocellular carcinoma more so inhibit immune cells that try to kill them, said UC San Diego School of Medicine Professor Dan Kaufman, M.D., Ph.D., lead author on the study, director of the Sanford Advanced Therapy Center at the universitys Sanford Stem Cell Institute and Moores Cancer Center member.

This is one key reason why some immunotherapies like CAR T cells have been less successful for solid tumors than for blood cancers the immunosuppressive tumor microenvironment.

Kaufman and his team produced stem cell-derived NK cells in which the receptor for transforming growth factor beta (TGF-) a protein that impairs immune function was disabled. HCC tumors and the liver in general contain copious amounts of the substance, which both inhibits the immune cell activity and allows cancer to proliferate.

They found that typical NK cells without the disabled receptor, like CAR T cells, were not very effective in battling the cancer. These are pretty resistant tumors when we put them in mice, they grow and kill the mice, he said. The five-year survival rate for HCC in humans is less than 20 percent.

When researchers tested the modified NK cells against the cancer, however, we got very good anti-tumor activity and significantly prolonged survival, he noted.

These studies demonstrate that it is crucial to block transforming growth factor beta at least for NK cells, but I also think its true for CAR T cells, Kaufman said. If you unleash NK cells by blocking this inhibitory pathway, they should kill cancer quite nicely.

Kaufman anticipates that his teams discovery will manifest itself in the clinical trials of many research groups and companies whether theyre working on CAR T-cell or NK-cell therapies, battling hepatocellular carcinoma or other challenging types of solid tumors.

Anyone developing such therapies for solid tumors should be working to inhibit transforming growth factor beta activity to improve cancer-killing and attain effective anti-tumor activity, he said.

Co-authors of this study include Jaya Lakshmi Thangaraj; Michael Coffey; and Edith Lopez, all of the Division of Regenerative Medicine at UC San Diegos School of Medicine.

This work was made possible by the NIH/NCI grants U01CA217885, P30CA023100 (administrative supplement), and the Sanford Stem Cell Institute at the University of California San Diego.

Disclosures: Kaufman is a co-founder and advisor to Shoreline Biosciences and has an equity interest in the company. He also consults VisiCELL Medical and RedC Bio, for which he receives income and/or equity. Studies in this work are not related to work of those companies. The terms of these arrangements have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. The remaining authors declare no competing interest.

The UC San Diego Sanford Stem Cell Institute (SSCI) is a global leader in regenerative medicine and a hub for stem cell science and innovation in space. SSCI aims to catalyze critical basic research discoveries, translational advances and clinical progress terrestrially and in space to develop and deliver novel therapeutics to patients.

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Stem Cell-Derived Therapy Shows Promise Against Treatment-Resistant Liver Cancer - University of California San Diego

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3-D image of a mouse kidney that has received human islet grafts. Beta cells are visible in green; red reveals the entire mouse kidney.

Credit: City of Hope/Mount Sinai Health System

LOS ANGELES and NEW YORK In preclinical studies, a team of researchers from City of Hope in Los Angeles and Mount Sinai Health System in New York reports new findings on a therapeutic combination that regenerated human insulin-producing beta cells,providing a possible new treatment for diabetes. The findings were published today in Science Translational Medicine.

This work, led by Andrew F. Stewart, M.D., Irene and Dr. Arthur M. Fishberg Professor of Medicine and Director of the Mount Sinai Diabetes, Obesity and Metabolism Institute, began at the Icahn School of Medicine at Mount Sinai in 2015. The studies were a team effort. Adolfo Garcia-Ocaa, Ph.D., formerly a professor at Mount Sinai who is now at City of Hope, a leading research center for diabetes and one of the largest cancer research and treatment organizations in the United States, and is the Ruth B. & Robert K. Lanman Chair in Gene Regulation and Drug Discovery Research and chair of theDepartment of Molecular & Cellular Endocrinology, and his research team designed the studies and performed the novel, extensive and detailed animal transplant and drug treatment models using beta cells from donors. Final studies took place at City of Hope in 2023.

For the study, the natural product harmine, which is found in some plants, was combined with a widely used class of type 2 diabetes therapy called GLP1 receptor agonists. Researchers transplanted a small number of human beta cells into mice that had no immune system and that also served as a standard model of type 1 and type 2 diabetes; these mice were treated with the combination therapy and their diabetes was rapidly reversed. Strikingly, human beta cell numbers increased by 700% over three months with this drug combination.

This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo. This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes, said Dr. Garcia-Ocaa, the papers corresponding author.

It has been remarkable to watch this story unfold over the past 15 years, said Dr. Stewart, who, along with Peng Wang, Ph.D., professor of Medicine (Endocrinology, Diabetes and Bone Disease) at Icahn Mount Sinai, conceived of and performed the initial high-throughput drug screen that led to the discovery of harmine described in Nature Medicine in 2015. The steady progression from the most basic human beta cell biology, through robotic drug screening and now moving to human studies, illustrates the essential role for physician-scientists in academia and pharma.

Growing new beta cells More than 10% of the worlds adult population has diabetes, a disease defined by high blood sugar levels. In both type 1 and type 2 diabetes, a reduction in both the quantity and quality of insulin-producing beta cells causes high blood sugar. Unfortunately, none of the many commonly used diabetes therapies are able to increase human beta cell numbers, and therefore cannot completely reverse diabetes.

Fortunately, most people with diabetes have some residual beta cells, which is what inspired the research team to search for ways to restore their numbers. The team had previously shown that several different inhibitors of an enzyme in beta cells called DYRK1A can induce the proliferation of adult human beta cells in a tissue culture dish for a few days. But prior to this study, no one had shown the ability to expand human beta cells numbers in vivo in human islet grafts used in an animal model over many months.

To accurately measure the mass of human beta cells in the islet grafts, the team turned to Sarah A. Stanley, M.B.B.Ch., Ph.D., associate professor of Medicine (Endocrinology, Diabetes and Bone Disease), and Neuroscience, at Icahn Mount Sinai. Using an advanced laser microscopy tool called iDISCO+ that effectively makes biological tissue transparent, Dr. Stanley saw that beta cell mass was dramatically increased through mechanisms that included enhanced proliferation, function and survival of the human beta cells. The technology allowed for accurate and rigorous quantitative assessment of engrafted human beta cells for the first time.

Translating results to the clinic The Mount Sinai team recently completed a phase 1 clinical trial of harmine in healthy volunteers to test its safety and tolerability. At the same time, Robert J. DeVita, Ph.D., professor of Pharmacological Sciences and director of the Marie-Jose and Henry R. Kravis Drug Discovery Institute at Mount Sinai, has developed next-generation DYRK1A inhibitors. Mount Sinai is conducting studies to test these in humans for potential toxicity risks and estimate dosing for clinical trials, and is planning to initiate first-in-human trials with independent research teams next year. Mount Sinai owns an extensive patent portfolio covering these technologies.

Researchers also want to address the fact that in patients with type 1 diabetes, the immune system will continue to kill new beta cells. At City of Hope, Dr. Garcia-Ocaa and colleague Alberto Pugliese, M.D., Samuel Rahbar Chair in Diabetes & Drug Discovery, chair of the Department of Diabetes Immunology and director of The Wanek Family Project for Type 1 Diabetes within the Arthur Riggs Diabetes & Metabolism Research Institute, plan to test inducers of beta cell regeneration together with immunomodulators that regulate the immune system. Their goal is for the combination to allow new beta cells to thrive and improve insulin levels.

Our studies pave the way for moving DYRK1A inhibitors into human clinical trials, and it's very exciting to be close to seeing this novel treatment used in patients, Dr. Garcia-Ocaa said. There is nothing like this available to patients right now.

The work outlined in the Science Translational Medicine paper was funded by grants from the National Institutes of Health (NIH), the National Institute of Diabetes and Digestive and Kidney Disease, and BreakthroughT1D (formerly JDRF), as well as from philanthropic donations to Mount Sinai, support from The Wanek Family Project for Type 1 Diabetesat City of Hope and additional generous philanthropic gifts.

Other critical members of the team include Mount Sinais Carolina Rosselot, Ph.D., Yansui Li, Ph.D., and Alexandra Alvarsson, Ph.D. Additional City of Hope authors on the paper are Geming Lu, M.D., assistant research professor, and Randy Kang, senior research associate, who are both members of Dr. Garcia-Ocaas lab.

Drs. Stewart and DeVita are named co-inventors on patent applications for DYRK1A inhibitors, such as harmine, for the treatment of diabetes. These patent applications are filed through the Icahn School of Medicine at Mount Sinai and are currently unlicensed.

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About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes.Founded in 1913,City of Hopehas grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis fornumerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hopes growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hopes affiliated group of organizations includesTranslational Genomics Research InstituteandAccessHopeTM. For more information about City of Hope, follow us onFacebook,X,YouTube,InstagramandLinkedIn.

About the Mount Sinai Health System Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our timediscovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweeks The Worlds Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals and by U.S. News & World Report's Best Hospitals and Best Childrens Hospitals. The Mount Sinai Hospital is on the U.S. News & World Report Best Hospitals Honor Roll for 2023-2024.

For more information, visithttps://www.mountsinai.org or find Mount Sinai onFacebook,Twitter andYouTube.

Science Translational Medicine

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The US Food and Drug Administration (FDA) has awarded a Regenerative Medicine Advanced Therapy (RMAT) designation to Longeverons Lomecel-B for treating mild Alzheimers Disease.

An RMAT designation provides the benefits of both fast track and breakthrough designations, thereby, allowing for accelerated approval based on surrogate or intermediate endpoints. It also allows for multiple meetings with the FDA to expedite drug development.

Following the news, Longeveron stock was up by over 20% in pre-market trading today, compared to the market close on 9 July.

Lomecel-B is made up of human mesenchymal stem cells, derived from the bone marrow of healthy human donors. It is being evaluated as a treatment for hypoplastic left heart syndrome, and ageing-related frailty, in addition to Alzheimers disease.

Lomecel-B met the primary safety endpoint in a Phase II CLERMIND trial (NCT05233774), which enrolled 50 patients with mild Alzheimers. There were three reported serious events within 30 days of Lomecel-B administration, one in each of three different treatment dose groups, compared to none in the placebo group.

There were no incidences of hypersensitivity, notable changes in laboratory evaluations and electrocardiogram (EKG), or cases of amyloid-related imaging abnormalities (ARIA). Additionally, no clinically asymptomatic microhaemorrhages were noted on MRI. The therapy also improved cognitive functions and reduced neuroinflammation assessed by diffusion tensor imaging, an MRI imaging technique.

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The global market for Alzheimers treatments is expected to be worth over $15.9bn in 2030, as per a GlobalData report. The field is dominated by amyloid-targeting therapies, with Eli Lillys Kisunla (donanemab) being the latest FDA-approved therapy in this class.

GlobalData is the parent company of Pharmaceutical Technology.

The news comes as a welcome reprieve for the company after it discontinued a Phase II trial of Lomecel-B in ageing-related frailty in Japan, in February. The decision was a strategic move by the Longeveron to focus on developing Lomecel-B in hypoplastic left heart syndrome, a rare congenital heart defect.

The company is evaluating Lomecel-B in a Phase IIb ELPIS II trial (NCT04925024) in hypoplastic left heart syndrome patients under 12 years of age. The trial plans to recruit 38 participants, with enrolment expected to be completed by the end of the year.

Stem cell treatments are a relatively new area in the Alzheimers treatment space. Regeneration Biomedical is evaluating its autologous stem cell treatment, RB-ADSC, in mild-to-moderate Alzheimers in a Phase I trial (NCT05667649).

Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva.

Editorial content is independently produced and follows thehighest standardsof journalistic integrity. Topic sponsors are not involved in the creation of editorial content.

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Longeveron scores RMAT designation for Alzheimers cell therapy - Pharmaceutical Technology

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), MITs research enterprise in Singapore, have developed a novel way to produce clinical doses of viable autologous chimeric antigen receptor (CAR) T-cells in a ultra-small automated closed-system microfluidic chip, roughly the size of a pack of cards.

This is the first time that a microbioreactor is used to produce autologous cell therapy products. Specifically, the new method was successfully used to manufacture and expand CAR-T cells that are as effective as cells produced using existing systems in a smaller footprint and less space, and using fewer seeding cell numbers and cell manufacturing reagents. This could lead to more efficient and affordable methods of scaling-out autologous cell therapy manufacturing, and could even potentially enable point-of-care manufacturing of CAR T-cells outside of a laboratory setting such as in hospitals and wards.

CAR T-cell therapy manufacturing requires the isolation, activation, genetic modification, and expansion of a patients own T-cells to kill tumor cells upon reinfusion into the patient. Despite how cell therapies have revolutionized cancer immunotherapy, with some of the first patients who received autologous cell therapies in remission for more than 10 years, the manufacturing process for CAR-T cells has remained inconsistent, costly, and time-consuming. It can be prone to contamination, subject to human error, and requires seeding cell numbers that are impractical for smaller-scale CAR T-cell production. These challenges create bottlenecks that restrict both the availability and affordability of these therapies despite their effectiveness.

In a paper titled A high-density microbioreactor process designed for automated point-of-care manufacturing of CAR T cells published in the journal Nature Biomedical Engineering, SMART researchers detailed their breakthrough: Human primary T-cells can be activated, transduced, and expanded to high densities in a 2-mililiter automated closed-system microfluidic chip to produce over 60 million CAR T-cells from donors with lymphoma, and over 200 million CAR T-cells from healthy donors. The CAR T-cells produced using the microbioreactor are as effective as those produced using conventional methods, but in a smaller footprint and less space, and with fewer resources. This translates to lower cost of goods manufactured (COGM), and potentially to lower costs for patients.

The groundbreaking research was led by members of the Critical Analytics for Manufacturing Personalized-Medicine (CAMP) interdisciplinary research group at SMART. Collaborators include researchers from the Duke-NUS Medical School; the Institute of Molecular and Cell Biology at the Agency for Science, Technology and Research; KK Womens and Childrens Hospital; and Singapore General Hospital.

This advancement in cell therapy manufacturing could ultimately offer a point-of-care platform that could substantially increase the number of CAR T-cell production slots, reducing the wait times and cost of goods of these living medicines making cell therapy more accessible to the masses. The use of scaled-down bioreactors could also aid process optimization studies, including for different cell therapy products, says Michael Birnbaum, co-lead principal investigator at SMART CAMP, associate professor of biological engineering at MIT, and a co-senior author of the paper.

With high T-cell expansion rates, similar total T-cell numbers could be attained with a shorter culture period in the microbioreactor (seven to eight days) compared to gas-permeable culture plates (12 days), potentially shortening production times by 30-40 percent. The CAR T-cells from both the microfluidic bioreactor and gas-permeable culture plates only showed subtle differences in cell quality. The cells were equally functional in killing leukemia cells when tested in mice.

This new method suggests that a dramatic miniaturization of current-generation autologous cell therapy production is feasible, with the potential of significantly alleviating manufacturing limitations of CAR T-cell therapy. Such a miniaturization would lay the foundation for point-of-care manufacturing of CAR T-cells and decrease the good manufacturing practice (GMP) footprint required for producing cell therapies which is one of the primary drivers of COGM, says Wei-Xiang Sin, research scientist at SMART CAMP and first author of the paper.

Notably, the microbioreactor used in the research is a perfusion-based, automated, closed system with the smallest footprint per dose, smallest culture volume and seeding cell number, as well as the highest cell density and level of process control attainable. These microbioreactors previously only used for microbial and mammalian cell cultures were originally developed at MIT and have been advanced to commercial production by Millipore Sigma.

The small starting cell numbers required, compared to existing larger automated manufacturing platforms, means that smaller amounts of isolation beads, activation reagents, and lentiviral vectors are required per production run. In addition, smaller volumes of medium are required (at least tenfold lower than larger automated culture systems) owing to the extremely small culture volume (2 milliliters; approximately 100-fold lower than larger automated culture systems) which contributes to significant reductions in reagent cost. This could benefit patients, especially pediatric patients who have low or insufficient T-cell numbers to produce therapeutic doses of CAR T-cells.

Moving forward, SMART CAMP is working on further engineering sampling and/or analytical systems around the microbioreactor so that CAR-T production can be performed with reduced labor and out of a laboratory setting, potentially facilitating the decentralized bedside manufacturing of CAR T-cells. SMART CAMP is also looking to further optimize the process parameters and culture conditions to improve cell yield and quality for future clinical use.

The research was conducted by SMART and supported by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) program.

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A new way to miniaturize cell production for cancer treatment - MIT News

University and community guests recently gathered to celebrate the 7,700 square-foot Good Manufacturing Practice facilitys grand opening in Hewitt Halls basement on the UC Irvine campus. Although the highly sterile environment remains off-limits for tours, the gala highlighted its importance to the campus, the UC system and the local community.

This facility is not just a building; it is a powerhouse of innovation and hope, meticulously designed and equipped to produce FDA-compliant cell and gene therapies, which are at the forefront of medical sciences promise for the future, says Dr. Michael J. Stamos, dean of the UC Irvine School of Medicine. It symbolizes our commitment to developing advanced treatments for neurological diseases and cancers that position us at the forefront of translational research, clinical trials and patient services, that were once deemed unattainable.

The facility is primarily dedicated to producing cell and gene products that meet stringent GMP regulations enforced by the FDA. In addition, researchers and scientists will use next-generation automated processing and manufacturing technologies, supplemented by leading-edge analytical tools, to produce the transformative therapies essential for clinical trials.

A collaborative effort

The School of Medicine, the Susan & Henry Samueli College of Health Sciences, the Sue & Bill Gross Stem Cell Research Center and the Chao Family Comprehensive Cancer Center and other campus partners have dedicated more than $12 million to the facility.

Our commitment to taking a multidisciplinary approach to integrating groundbreaking research with clinical applications was also recognized and supported by the California Institute for Regenerative Medicine, says Aileen Anderson, Ph.D., director of the UC Irvine Stem Cell Research Center and professor of physical medicine & rehabilitation. We were awarded an initial two-year, $2 million grant to help launch this project, along with membership in the prestigious CIRM Cell and Gene Therapy Manufacturing Network.

Next-generation treatments

The GMP facility has a seven-room cellular therapy and viral vector production area, an adjacent quality control laboratory, and a storage warehouse for raw and finished products. It is designed to create FDA-approved stem cell, engineered chimeric antigen receptor T-cell and gene products for clinical research and treatment across multiple medical disciplines.

These potentially pioneering therapies require meticulous production and processing to meet the complex needs of current clinical trials, enhance delivery and improve patient outcomes. They target a range of conditions, including neurological diseases, spinal cord injuries, autoimmune diseases like multiple sclerosis and lupus, and cancers such as leukemia and lymphoma.

Workforce development

In addition to advancing treatment options, the facility will provide educational opportunities and hands-on experience in GMP processes to prepare the next generation of scientists and clinicians who will lead the development of innovations in regenerative medicine.

By fostering interdisciplinary collaboration, investing in state-of-the-art technology and focusing on comprehensive training, our new facility demonstrates the universitys commitment to translational research and clinical excellence that will offer new treatment options for patients worldwide who will benefit from these groundbreaking discoveries, Stamos says.

If you want to learn more about supporting this or other activities at UC Irvine, please visit the Brilliant Future website. By engaging 75,000 alumni and garnering $2 billion in philanthropic investment, UC Irvine seeks to reach new heights of excellence instudent success,health and wellness, research and more. The School of Medicine plays a vital role in the success of the campaign. Learn more by visiting https://brilliantfuture.uci.edu/uci-school-of-medicine/.

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Advancing regenerative medicine therapies UCI News - UCI News

Cell Therapy Market Outlook

The cell therapy market was valued at USD 16.30 billion in 2023, driven by the rising burden of chronic diseases and increased funding for cell therapy clinical studies across the globe. The market is expected to grow at a CAGR of 18.1% during the forecast period of 2024-2032, with the values likely to reach USD 72.84 billion by 2032.

Cell Therapy: Introduction

Cell therapy is a cutting-edge biomedical technology that involves the transplantation of human cells to replace or repair damaged tissues and organs, offering promising treatments for a variety of diseases and injuries. Utilizing stem cells, immune cells, and other specialized cells, this innovative approach targets conditions such as cancer, cardiovascular diseases, neurodegenerative disorders, and autoimmune diseases. By harnessing the body's intrinsic healing mechanisms, cell therapy aims to restore normal function, improve patient outcomes, and enhance quality of life. Rapid advancements in research and clinical trials continue to expand its potential, positioning cell therapy at the forefront of personalized medicine and regenerative healthcare.

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Key Trends in the Global Cell Therapy Market

Key trends in the global cell therapy market include:

Advancements in Manufacturing: Continuous improvements in cell manufacturing processes, including automation and scalability, are enhancing production efficiency and reducing costs.

Regulatory Developments: Evolving regulatory frameworks are shaping the landscape of cell therapy development and commercialization, with efforts to streamline approval processes and ensure patient safety. Increasing Investment: Rising investment from both public and private sectors is fueling research and development activities, driving innovation and expanding the scope of cell therapy applications.

Expansion of Indications: Cell therapies are being explored for a growing range of indications beyond oncology, including cardiovascular diseases, autoimmune disorders, and degenerative conditions. Collaboration and Partnerships: Collaborative efforts between industry players, academic institutions, and government agencies are facilitating knowledge sharing, resource pooling, and the acceleration of clinical development programs.

Personalized Medicine: Advances in cell characterization and patient-specific therapies are enabling the development of personalized treatment approaches tailored to individual genetic profiles and disease characteristics. Commercialization Challenges: Despite promising clinical outcomes, challenges such as reimbursement issues, manufacturing complexities, and market access barriers continue to pose hurdles to the widespread adoption and commercial success of cell therapies. Global Market Expansion: The global cell therapy market is witnessing geographical expansion, with increasing adoption and investment in emerging markets, particularly in Asia-Pacific regions.

Integration of Cell Therapy with Other Modalities: Integration of cell therapy with complementary treatment modalities, such as gene editing and tissue engineering, is unlocking new therapeutic possibilities and synergistic effects. Patient Access and Affordability: Efforts to address concerns related to patient access, affordability, and equitable distribution of cell therapies are gaining prominence, with initiatives aimed at improving healthcare infrastructure and increasing affordability for patients worldwide. Cell Therapy Market Segmentation

Market Breakup by Type

Stem Cell Bone Marrow Derived Mesenchymal Stem Cell Hematopoietic Stem Cells Umbilical Cord Derived Stem Cell Adipose Derived Stem Cell Skin Stem Cells Induced Pluripotent Stem Cells Others Non-Stem Cell (Dendritic Cell, CART-Cell)

Market Breakup by Type of Therapy

Autologous Allogeneic

Market Breakup by Therapeutic Area

Musculoskeletal Disorders Cardiovascular Diseases Neurological Disorders Oncological Disorders Dermatology Inflammatory and Autoimmune Disorders Others

Market Breakup by End User

Hospitals and Clinics Regenerative Medicine Centers Diagnostic and Research Centers Others

Market Breakup by Region

North America Europe Asia Pacific Latin America Middle East and Africa

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Cell Therapy Market Overview

The global cell therapy market is experiencing significant growth, driven by advancements in biomedical research, increasing prevalence of chronic diseases, and a rising focus on personalized medicine. Cell therapy, which involves the transplantation of human cells to repair or replace damaged tissues and organs, has emerged as a revolutionary approach in treating various conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and autoimmune diseases.

North America holds a dominant position in the cell therapy market, primarily due to robust healthcare infrastructure, high investment in research and development, and supportive regulatory frameworks. The United States, in particular, is a key player, with numerous biotech companies, research institutions, and clinical trials contributing to the market's expansion. The presence of well-established healthcare facilities and increasing awareness about advanced therapies among patients further bolster the market in this region.

Europe is another significant market for cell therapy, characterized by strong government support and extensive research activities. Countries like Germany, the United Kingdom, and France are leading contributors, driven by a high prevalence of chronic diseases and a growing elderly population. The European Medicines Agency (EMA) provides a conducive regulatory environment, encouraging the development and commercialization of innovative cell-based treatments. Additionally, collaborations between academic institutions and biopharmaceutical companies are propelling market growth in Europe.

The Asia Pacific region is witnessing rapid growth in the cell therapy market, fueled by increasing investments in healthcare infrastructure, rising disposable incomes, and growing awareness about advanced medical treatments. Countries such as Japan, China, and South Korea are at the forefront, with substantial government funding and strategic initiatives to promote regenerative medicine. Japan, in particular, has been a pioneer in cell therapy, with a strong focus on research and clinical applications. The region's large patient pool, coupled with an expanding biotechnology sector, presents significant opportunities for market players.

In Latin America, the cell therapy market is gradually gaining traction, driven by improving healthcare facilities and growing investments in medical research. Brazil and Mexico are key markets in this region, with an increasing number of clinical trials and research programs aimed at exploring the potential of cell-based therapies. Despite facing challenges such as limited funding and regulatory hurdles, the region is poised for growth as awareness about cell therapy continues to rise and technological advancements become more accessible.

The Middle East and Africa region is also emerging as a potential market for cell therapy, albeit at a slower pace compared to other regions. Countries like Israel, the United Arab Emirates, and South Africa are investing in healthcare infrastructure and research initiatives to explore the benefits of regenerative medicine. However, the market's growth in this region is hindered by economic constraints, limited access to advanced medical technologies, and regulatory challenges. Nevertheless, ongoing efforts to improve healthcare services and increasing international collaborations are expected to drive future growth in the cell therapy market.

Cell Therapy Market: Competitor Landscape

The key features of the market report include patent analysis, grants analysis, clinical trials analysis, funding and investment analysis, partnerships, and collaborations analysis by the leading key players. The major companies in the market are as follows:

Vericel Corporation

Vericel Corporation is a biopharmaceutical company specializing in advanced cell therapies for the treatment of serious medical conditions. Headquartered in the United States, Vericel focuses on developing innovative therapies derived from a patient's own cells to address unmet needs in areas such as orthopedics and dermatology. Their flagship products include MACI, a cell-based treatment for cartilage defects in the knee, and Epicel, a cultured epidermal autograft for severe burns. With a commitment to scientific excellence and patient care, Vericel continues to advance the field of regenerative medicine through research, development, and commercialization of transformative cell-based therapies.

Kolon TissueGene Inc.

Kolon TissueGene Inc is a biotechnology company specializing in regenerative medicine and cell therapy. Founded in South Korea, it focuses on developing innovative treatments for orthopedic and neurological disorders. The company's flagship product, Invossa, is the world's first cell-mediated gene therapy for osteoarthritis, offering a potentially transformative approach to disease management. Kolon TissueGene Inc is committed to advancing the field of regenerative medicine through cutting-edge research, strategic partnerships, and a dedication to improving patient outcomes. With a focus on addressing unmet medical needs, the company aims to revolutionize the treatment landscape for a range of debilitating conditions.

JCR Pharmaceuticals Co. Ltd

JCR Pharmaceuticals Co. Ltd is a leading biopharmaceutical company based in Japan, specializing in the development, manufacturing, and commercialization of innovative therapeutics and medical devices. With a focus on rare diseases, oncology, and regenerative medicine, JCR Pharmaceuticals is committed to advancing healthcare through cutting-edge research and development efforts. The company leverages its expertise in biologics and recombinant protein technologies to bring novel treatments to patients worldwide. Through strategic partnerships and collaborations, JCR Pharmaceuticals aims to address unmet medical needs and improve the quality of life for patients across a wide range of therapeutic areas.

MEDIPOST Co. Ltd.

MEDIPOST Co. Ltd. is a leading biotechnology company headquartered in South Korea, specializing in the development and commercialization of innovative cell therapies. Founded in 2000, MEDIPOST focuses on utilizing mesenchymal stem cells (MSCs) derived from umbilical cord blood for therapeutic applications. The company's flagship product, CARTISTEM, is an allogeneic MSC-based therapy used for the treatment of osteoarthritis. MEDIPOST is committed to advancing the field of regenerative medicine through cutting-edge research, strategic partnerships, and a dedication to improving patient outcomes. With a strong emphasis on quality, safety, and efficacy, MEDIPOST continues to be at the forefront of cell therapy innovation globally.

Osiris (Mesoblast)

Osiris Therapeutics, now part of Mesoblast, is a pioneering biotechnology company focused on developing innovative cell-based therapies. Specializing in regenerative medicine, Osiris/Mesoblast has made significant strides in leveraging mesenchymal stem cells (MSCs) for treating a variety of medical conditions, including orthopedic disorders, inflammatory diseases, and cardiovascular conditions. Their flagship product, TEMCELL, is approved for graft-versus-host disease (GVHD) in Japan. The company's research pipeline continues to explore the therapeutic potential of MSCs across diverse therapeutic areas, positioning Osiris/Mesoblast as a key player in the field of cell therapy and regenerative medicine.

Other key players in the market include Stemedica Cell Technologies Inc., ImmunoACT, Castle Creek Biosciences, Inc., PHARMICELL Co. Ltd, ANTEROGEN.CO.LTD, Novartis AG, Celgene Corp. (Bristol-Myers Squibb Company), Allogene Therapeutics Inc., and Stempeutics Research Pvt. Ltd.

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Cell Therapy Market Size, Share, Growth, Report and Forecast 2024-2032 - openPR

image:

The kidney contains macula densa cells (green/yellow), which orchestrate kidney regeneration. The circulating plasma is labeled white/gray, and all kidney cells are labeled by their production of genetically inserted green and red fluorescent proteins

Credit: Georgina Gyarmati, MD, PhD Zilkha Neurogenetic Institute

A loss of salt and body fluid can stimulate kidney regeneration and repair in mice, according to a NIH-funded study led by USC Stem Cell scientist Janos Peti-Peterdi and published inThe Journal of Clinical Investigation. This innate regenerative response relies on a small population of kidney cells in a region known as the macula densa (MD), which senses salt and exerts control over filtration, hormone secretion, and other key functions of this vital organ.

Our personal and professional mission is to find a cure for kidney disease, a growing global epidemic affecting one out of seven adults, which translates to 850 million people worldwide or about 2 million in the Los Angeles area, said Peti-Peterdi,a professor of physiology, neuroscience and medicine at theKeck School of Medicine of USC. Currently, there is no cure for this silent disease. By the time kidney disease is diagnosed, the kidneys are irreversibly damaged and ultimately need replacement therapies, such as dialysis or transplantation.

To address this growing epidemic, Peti-Peterdi, first author Georgina Gyarmati, and their colleagues took a highly non-traditional approach. As opposed to studying how diseased kidneys fail to regenerate, the scientists focused on how healthy kidneys originally evolved.

From an evolutionary biology perspective, the primitive kidney structure of the fish turned into more complicated and more efficiently working kidneys to absorb more salt and water, said Peti-Peterdi, who also directs the Multi-Photon Microscopy Core at the Zilkha Neurogenetic Institute (ZNI). This was necessary for adaptation to the dry land environment when the animal species moved from the salt-rich seawater. And thats why birds and mammals have developed MD cells and this beautiful, bigger, and more efficient kidney structure to maintain themselves and functionally adapt to survive. These are the mechanisms that we are targeting and trying to mimic in our research approach.

With this evolutionary history in mind, the research team fed lab mice a very low salt diet, along with a commonly prescribed drug called an ACE inhibitor that furthered lowered salt and fluid levels. The mice followed this regimen for up to two weeks, since extremely low salt diets can trigger serious health problems if continued long term.

In the region of the MD, the scientists observed regenerative activity, which they could block by administering drugs that interfered with signals sent by the MD. This underscored the MDs key role in orchestrating regeneration.

When the scientists furthered analyzed mouse MD cells, they identified both genetic and structural characteristics that were surprisingly similar to nerve cells. This is an interesting finding, because nerve cells play a key role in regulating the regeneration of other organs such as the skin.

In the mouse MD cells, the scientists also identified specific signals from certain genes, including Wnt, NGFR, and CCN1, which could be enhanced by a low-salt diet to regenerate kidney structure and function. In keeping with these findings in mice, the activity of CCN1 was found to be greatly reduced in patients with chronic kidney disease (CKD).

To test the therapeutic potential of these discoveries, the scientists administered CCN1 to mice with a type of CKD known asfocal segmental glomerulosclerosis.They also treated these mice with MD cells grown in low-salt conditions. Both approaches were successful, with the MD cell treatment producing the biggest improvements in kidney structure and function. This might be due to the MD cells secreting not only CCN1, but also additional unknown factors that promote kidney regeneration.

We feel very strongly about the importance of this new way of thinking about kidney repair and regeneration, said Peti-Peterdi. And we are fully convinced that this will hopefully end up soon in a very powerful and new therapeutic approach.

Additional co-authors are Urvi Nikhil Shroff, Anne Riquier-Brison, Dorinne Desposito, Audrey Izuhara, Sachin Deepak, Alejandra Becerra Calderon, James L. Burford, Hiroyuki Kadoya, Ju-Young Moon, Yibu Chen, Nariman Ahmadi, Berislav V. Zlokovic, and Inderbir S. Gill from USC; Wenjun Ju and Matthias Kretzler from the University of Michigan; Sean D. Stocker from the University of Pittsburgh School of Medicine; Markus M. Rinschen from the University of Cologne; Lester Lau from the University of Illinois at Chicago; Daniel Biemesderfer from Yale University School of Medicine; Aaron W. James from Johns Hopkins University; and Liliana Minichiello from the University of Oxford.

This work was federally funded by the National Institutes of Health (grants DK064324, DK123564, DK135290, S10OD021833, and 2P30-DK-081943) and further supported by an American Heart Association predoctoral research fellowship (grant 19PRE34380886).

Disclosure: Peti-Peterdi andGyarmatiare cofounders of Macula Densa Cell LLC, a biotechnology company that develops therapeutics to target MD cells for a regenerative treatment for CKD. Macula Densa Cell LLC has a patent entitled Targeting macula densa cells as a new therapeutic approach for kidney disease (US patents 10,828,374 and 11,318,209). Gill declares equity interest in OneLine Health and Karkinos.

Journal of Clinical Investigation

Experimental study

Animals

Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney

10-Apr-2024

Peti-Peterdi and Gyarmati are cofounders of Macula Densa Cell LLC, a biotechnology company that develops therapeutics to target MD cells for a regenerative treatment for CKD. Macula Densa Cell LLC has a patent entitled Targeting macula densa cells as a new therapeutic approach for kidney disease (US patents 10,828,374 and 11,318,209). Gill declares equity interest in OneLine Health and Karkinos.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Link:
To regenerate the kidney, please don't pass the salt - EurekAlert

In an extremely rare case, a patient who received a cell-based cancer treatment later developed a second cancer that arose from the treatment itself.

Known as chimeric antigen receptor (CAR) T-cell therapy, the treatment involves harvesting a patient's immune cells and genetically modifying them to target and attack specific types of cancers, including lymphomas, leukemias and multiple myeloma. For many people, the treatment has been life-changing however, as the first CAR T-cell therapy was only approved in 2017, scientists are still learning about the treatment's benefits and risks.

Secondary cancers are known to occur in 4% to 16% of people following chemotherapy and radiation therapy, but so far, only about 20 cases of T-cell cancer after CAR T therapy have been reported to the Food and Drug Administration (FDA) Adverse Events Reporting System database. Given that more than 34,000 people in the U.S. have received the treatment, CAR-related secondary cancers appear quite rare.

Despite the low risk, these sporadic cases have drawn scrutiny from the FDA and left the research community with unanswered questions about the underlying causes and potential risk of CAR-related secondary cancers. The FDA maintains that the overall benefit of these therapies outweighs potential risks, but the agency wants to better understand the risks, nonetheless.

Related: In a 1st, scientists use designer immune cells to send an autoimmune disease into remission

Now, a new case study, published Tuesday (June 12) in The New England Journal of Medicine, provides important insight into secondary cancers that may arise following CAR T-cell therapy.

The report details the case of a 71-year-old woman with a history of multiple myeloma, a type of cancer that affects immune cells in the blood. The patient developed severe gastrointestinal symptoms four months after receiving CAR T-cell therapy. Upon further investigation, her doctors found that she had developed a new cancer in her intestinal tract.

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The tumor was CAR-positive, indicating that the cancer had arisen from one of the immune cells modified for the woman's treatment.

"In the case of this patient, what is called a helper T cell, an essential infection-fighting cell, unexpectedly was the culprit," first study author Dr. Metin Ozdemirli, a professor of pathology at Georgetown University School of Medicine and attending physician and director of hematopathology and hematology laboratories at MedStar Georgetown University Hospital, said in a statement.

However, it's not clear whether modifying the T cell actually caused the secondary cancer to develop or whether the cell was already precancerous or cancerous and the introduction of CAR was irrelevant, Dr. Paul Maciocia, a consultant hematologist and clinician scientist who specializes in CAR T-cell therapy at University College London and was not involved in the case, told Live Science in an email.

A closer look at the woman's tumor revealed that the CAR-positive cancer cells had unusual changes in their genetic material. These changes likely arose as a result of the CAR-T modification process, during which a virus is used to randomly inject new DNA into the genome of the harvested immune cells. This modification enables the cells to seek out and kill cancer when they are reintroduced into the patient.

In the case of the 71-year-old woman, however, researchers did not find any significant genetic changes that would directly explain why the CAR T cells became cancerous.

The risk of secondary cancers in a given patient is difficult to gauge because everyone's genome is unique and the gene insertion by viruses in CAR-T is random, said Leonardo Ferreira, an assistant professor of immunology at the Medical University of South Carolina who was not involved in the research. Thus, the case study makes a powerful argument for analyzing the DNA of CAR T cells before infusing them into the patient, Ferreira told Live Science in an email. This final check could help clinicians ensure they're not introducing potentially cancerous cells back into the body.

Scientists could also explore more targeted approaches to tweaking immune cells, such as using CRISPR-Cas9, Ferreira added. In the woman's case, it's unclear whether the modification process pushed her cells to become cancerous but a more-precise DNA editing approach may reduce the chance of that happening.

For now, it's crucial to emphasize that these secondary cancers are extremely rare.

"While vigilance is essential with a new class of therapy, patients, physicians and regulators should in my view not be unduly concerned about the risk of CAR-positive T-cell lymphoma," Maciocia said. "For almost all CAR-T recipients, the potentially life-saving benefit of CAR-T is likely to outweigh this risk."

Editor's note: This article was updated shortly after publishing to update Leonardo Ferreira's job title and affiliation.

This article is for informational purposes only and is not meant to offer medical advice.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!

Original post:
Immunotherapy to treat cancer gave rise to 2nd cancer in extremely rare case - Livescience.com

Pictured: 3D illustration of a CAR-T cell attacking a cancer cell/iStock, Meletios Verras

Despite warnings about the drug class from the FDA, a large study led by Stanford Medicine has found that CAR-T cell therapies carry only a low risk of secondary malignancies.

The results, published Wednesday in The New England Journal of Medicine, come from a review of 724 patients who had undergone CAR-T therapies at Stanford Health Care between 2016 and 2024. Overall, the study found that secondary cancers arose in approximately 6.5% of patients over a median follow-up period of three years.

According to Stanfords announcement on Wednesday, this incidence rate was roughly similar to patients who had been treated instead with stem cell therapy.

The study identified one patient who died due to a secondary T-cell cancer, though Stanford researchers contend this was likely caused by the immunosuppression associated with CAR-T therapies, rather than a mis-insertion of the gene for the CAR construct during the preparation of the treatment.

Deep profiling of both the original and secondary cancers found that they had distinct immunophenotypes and genomic profiles, according to researchers, suggesting that that the CAR-T therapy was not responsible for the secondary malignancy.

These results may help researchers focus on the immune suppression that can precede and often follows CAR-T therapy, David Miklos, co-senior author of the study and chief of bone marrow transplantation and cell therapy at Stanford, said in a statement.

Understanding how immunosuppression aggravates cancer risk after CAR-T treatment is especially important as the CAR-T cell field pivots from treating high-risk, refractory blood cancers to lower risk, but clinically important, disorders including autoimmune diseases, Miklos said.

Stanfords findings echo that of Penn Medicine, which in January 2024 published a paper in Nature Medicine that also found a low risk of secondary cancers after CAR-T treatment.

The Penn researchers used a smaller sample size449 patientsbut their figures were similar: Over a median follow-up of 10.3 months, only 16 patients developed secondary cancers, most of which were solid tumors such as skin and prostate cancer. There was only one case of secondary T-cell lymphoma, which showed only very low levels of the CAR transgene.

The respective findings from Stanford and Penn could help allay some concerns about the safety of CAR-T therapies. In November 2023, the FDA announced that it was investigating the drug class after it identified cases of secondary malignancies in patients who had received approved CAR-T products. The probe pushed the regulator in April 2024 to require a class-wide black box warning flagging the risk.

All six commercially available CAR-T therapies were impacted including Gileads Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel), Bristol Myers Squibbs Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Novartis Kymriah (tisagenlecleucel) and Johnson & Johnsons Carvykti (ciltacabtagene autoleucel).

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Read more from the original source:
Secondary Cancer Risk Is Low After CAR T Cell Treatment: Stanford Study - BioSpace

This article originally appeared on Targeted Oncology.

Patients with advanced renal cell carcinoma (RCC) who received nivolumab (Opdivo; Bristol Myers Squibb) plus cabozantinib (Cabometyx; Exelixis) in the first line achieved a longer treatment-free survival (TFS) vs sunitinib (Sutent; Pfizer), according to data from an analysis of the phase 3 CheckMate 9ER trial (NCT03141177) presented duringASCO 2024.1

CheckMate 9ER was an open-label study that enrolled patients with histologically confirmed untreated advanced or metastatic clear cell RCC who did not receive prior systemic therapy for RCC.

Over the 48-month period following random assignment, patients in the intention-to-treat (ITT) population who received the combination (n = 323) experienced a mean TFS of 7.0 months compared with 4.6 months (95% CI, 0.8-3.9) in the sunitinib arm (n = 328), for a difference of 2.4 months (95% CI, 0.8-3.9). Patients without a grade 2 or higher treatment-related adverse effect (TRAE) experienced a mean TFS of 3.0 months vs 2.3 months, respectively; those who experienced a grade 2 or higher TRAE experienced a mean TFS of 3.9 months vs 2.3 months. The 48-month mean overall survival (OS) was 35.1 months in the doublet arm vs 30.7 months in the sunitinib arm. The mean times on protocol treatment were 22.6 and 14.1 months, respectively.

Additionally, the 48-month OS rates were 49.2% in the nivolumab plus cabozantinib arm vs 40.2% in the sunitinib arm, and the 48-month TFS rates were 33.3% compared with 12.9%, respectively.

There are multiple immunotherapy-based combination treatments with similar efficacies approved for first-line treatment of advanced RCC. Therefore, its important to characterize patient survival time after treatment initiation, Charlene Mantia, MD, a medical oncologist at Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School in Boston, Massachusetts, said during a presentation of the findings. Over the 4-year period since first-line protocol therapy initiation, [patients treated with] nivolumab plus cabozantinib achieved a 1.5-times longer mean TFS vs sunitinib.

CheckMate 9ER was an open-label study that enrolled patients with histologically confirmed untreated advanced or metastatic clear cell RCC who did not receive prior systemic therapy for RCC. However, treatment with 1 prior adjuvant or neoadjuvant therapy was permitted for patients with completely resectable disease if the agent was not VEGF targeted and if recurrence occurred at least 6 months following treatment.2,3

Patients were randomly assigned 1:1 to receive intravenous nivolumab 240 mg every 2 weeks in combination with oral cabozantinib 40 mg daily or sunitinib 50 mg daily for 4 weeks in 6-week cycles. Treatment in both arms continued until disease progression or unacceptable toxicity, and the maximum duration of nivolumab therapy was 2 years.

The primary end point was progression-free survival by blinded independent central review per RECIST 1.1 criteria. Secondary end points included OS, objective response rate, and safety.

In the ITT population, the baseline characteristics were well balanced between the combination and sunitinib arms; the median (IQR) age was 62 (29-90) years vs 61 (28-86) years, respectively. Most patients in both arms were not from North America or Europe (51.1% vs 50.9%), had a Karnofsky performance status (KPS) of 90 or 100 (79.6% vs 73.5%), underwent prior nephrectomy (68.7.% vs 71.0%), and had tumors without sarcomatoid features (89.1% vs 87.1%).2

Additional findings from the TFS analysis showed that patients with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable-risk disease in the combination (n = 74) and control (n = 72) arms achieved a 48-month mean TFS of 6.1 months vs 4.3 months, respectively, for a difference of 1.8 months (95% CI, 1.1 to 4.6). The mean OS during this time was 38.2 months in the nivolumab plus cabozantinib arm vs 38.6 months in the sunitinib arm. Patients spent a mean time of 25.2 months vs 19.9 months on protocol treatment, respectively.1

Further, patients with IMDC intermediate- or poor-risk disease in the combination (n = 249) and sunitinib (n = 256) arms achieved a 48-month mean TFS of 7.2 months vs 4.7 months, respectively, for a difference of 2.5 months (95% CI, 0.8-4.3). The 48-month mean OS was 34.2 months vs 28.5 months, respectively, and patients spent a mean time of 21.8 months in the combination arm vs 12.5 months in the sunitinib arm on protocol treatment.

Results from a TFS subgroup analysis showed that the benefit with nivolumab plus cabozantinib vs sunitinib was observed across prespecified subgroups. The largest differences in 48-month mean TFS in favor of the combination were reported among patients with a KPS of 80 or less (5.3 months; 95% CI, 2.1-8.5), IMDC poor-risk disease (4.0 months; 95% CI, 0.5-7.5), and a PD-L1 expression of at least 1% (3.5 months; 95% CI, 0.8-6.1).

Mean TFS differences were similarly longer for nivolumab plus cabozantinib vs sunitinib across most baseline subgroups analyzed, Mantia said in conclusion. TFS was more frequently observed after patients stopped therapy due to adverse effects, study drug toxicity, or prespecified other reasons with nivolumab plus cabozantinib vs sunitinib. We believe that future studies should continue to investigate the impact of having a defined treatment duration for patients. This partitioned OS analysis highlights important aspects of patient survival time that can be considered in making decisions when choosing a first-line treatment for patients.

References

1. Mantia C, Jegede O, Viray H, et al. Partitioned overall survival: Comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma (aRCC). J Clin Oncol.2024;42(suppl 16):4507. doi:10.1200/JCO.2024.42.16_suppl.4507

2. Powles T, Burotto M, Escudier B, et al. Nivolumab plus cabozantinib versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended follow-up from the phase III randomised CheckMate 9ER trial.ESMO Open. 2024;9(5):102994. doi:10.1016/j.esmoop.2024.102994

3. A study of nivolumab combined with cabozantinib compared to sunitinib in previously untreated advanced or metastatic renal cell carcinoma (CheckMate 9ER). ClinicalTrials.gov. Updated January 17, 2024. Accessed June 13, 2024. https://clinicaltrials.gov/study/NCT03141177

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Treatment-Free Survival Extended With Nivolumab/Cabozantinib in Advanced Renal Cell Carcinoma - AJMC.com Managed Markets Network