Researchers develop scalable method to generate key immune cells for cancer therapy
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Researchers at the Center for Regenerative Medicine (CReM) at Boston Medical Center (BMC) and Boston University (BU) have developed a scalable method for generating CD4+ helper T cells from induced pluripotent stem cells (iPSCs), overcoming a longstanding challenge in the development of stem cell-based immunotherapies. The findings, published in Stem Cell Reports, could help advance efforts to create off-the-shelf CAR-T cell therapies that can be produced at scale and made more readily available to patients.
CAR-T cell therapy works by isolating a patient's T cells, genetically modifying them to recognize and target cancer cells, and returning them to the patient. While the approach has transformed treatment for some blood cancers, producing a personalized therapy for each patient can be costly and time-intensive.
iPSCs, which are generated from donated adult skin or blood cells, could enable the large-scale production of T cells that could be used "off the shelf" for many patients rather than being made individually for each one. A key challenge, however, has been reliably generating functional CD4+ helper T cells, which play an important role in coordinating and regulating immune responses.
A team of researchers led by Gustavo Mostoslavsky, M.D., Ph.D., co-director of the CReM and professor of medicine and virology, immunology and microbiology at BU Chobanian & Avedisian School of Medicine, and doctoral student Julian Amirault found the key to producing CD4+ cells lies in a molecular signaling pathway called Notch.
While Notch signaling is critical to early T cell development, the researchers found that removing it during later stages of maturation, while simultaneously reducing anti-T cell receptor signaling, allowed developing cells to survive and mature into CD4+ T cells at scale.
"Our protocol is simple, straightforward, and potentially scalable for treatment," Mostoslavsky said. "And our system is making T cells that look like those from blood, with a full repertoire of the different subtypes."
Beyond the clinical implications, the work has also shed new light on T cell biology, revealing how Notch signaling shifts over time to direct cells toward either the CD8 or the CD4 lineage. With a workable protocol in hand, the team's next step is to introduce the chimeric antigen receptor (CAR) directly into their iPSC-derived CD4+ and CD8+ cells and test their ability to kill cancer in animal models, an important next step toward the potential development of universal CAR-T therapies.
"What we have developed represents a major advance in how the future of CAR-T could be done," said Mostoslavsky. "The potential is that one day, these cells could be ready and waiting when a patient is diagnosed. No cell collection, no individualized manufacturing, just treatment."
Publication details
Generation of effector CD4+ T cells from human iPSC, Stem Cell Reports (2026). DOI: 10.1016/j.stemcr.2026.103058. www.cell.com/stem-cell-reports … 2213-6711(26)00269-9
Journal information: Stem Cell Reports
Key medical concepts
Induced Pluripotent Stem CellsNotch Proteolysis and Signaling Pathway
Clinical categories
OncologyAllergy and immunology Provided by Boston Medical Center Who's behind this story?
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