CAR-T therapies can be transformative against certain cancers, but they’re slow and costly to make — each dose is manufactured from an individual patient’s own immune cells. New research points to a way around that bottleneck: growing the needed cells from stem cells, at scale.
Researchers at Boston University’s Center for Regenerative Medicine and Boston Medical Center found that manipulating Notch signaling lets them reliably produce CD4+ helper T cells from induced pluripotent stem cells (iPSCs). The trick: removing Notch signaling during later maturation while dialing down another signal, which allows the developing cells to survive and mature into functional, diverse CD4+ T cells resembling those in blood. The work appeared in Stem Cell Reports.
Why off-the-shelf matters
Today’s CAR-T requires isolating and re-engineering each patient’s T cells — expensive and time-consuming. iPSC-derived cells could enable universal, ready-made (“off-the-shelf”) therapies, produced in advance and available on demand. Helper (CD4+) T cells are an important piece: they support and sustain the immune attack that killer cells carry out. “T cells that look like those from blood, with a full repertoire of the different subtypes,” is how principal investigator Gustavo Mostoslavsky described the output.
Why it matters — and what’s next
Reliable, scalable production of functional T cells from stem cells is a key hurdle for the whole off-the-shelf cell-therapy field. The team plans to add chimeric antigen receptors (CARs) to their iPSC-derived cells and test them in animal models — so this is an early, preclinical advance, not a therapy yet.