Boston University researchers reported a scalable method to generate CD4+ helper T cells from induced pluripotent stem cells (iPSCs) using a Notch signaling strategy. In a Stem Cell Reports study, the team described producing effector CD4+ populations by modulating Notch during later maturation stages while reducing anti–T cell receptor signaling. The approach targets a key bottleneck in off-the-shelf CAR T manufacturing: producing functional helper CD4 cells reliably, at scale, with the right subtype repertoire. The work also suggests that shifting Notch timing can influence lineage outcomes between CD4 and CD8 differentiation. The group’s next step is to introduce CAR constructs into iPSC-derived CD4+ and CD8+ cells and test tumor-killing activity in animal models, aiming for universal or rapidly available cellular therapies.