Memory programming and new manufacturing paradigms in CAR-T cell therapy

The therapeutic efficacy of chimeric antigen receptor (CAR) T cells is often constrained by their limited persistence in vivo. Accordingly, numerous strategies have been developed to prolong CAR-T cell survival, many of which leverage memory-like phenotypes to sustain anti-tumor activity. However, extended persistence can also exacerbate CAR-T cell-related toxicities in certain malignancies, underscoring the need for context-specific approaches. Moreover, the rapid advancement of "off-the-shelf" CAR-T platforms may diminish the necessity for engineering enhanced persistence, enabling timely and broadly accessible therapies. In this review, we discuss recent advances aimed at augmenting CAR-T cell persistence with an emphasis on memory-associated features, and highlight emerging technologies that promise to deliver ready-to-use CAR-T products while mitigating the need for further persistence-focused modifications.