UCLA

Adoptive T-cell therapy utilizing chimeric antigen receptors (CARs) has shown multiple successes in treating certain hard-to-treat blood cancers, leading to five CAR T-cell therapies approved by the FDA for leukemia, lymphoma, and multiple myeloma. Despite such successes, there remain several obstacles including antigen escape and severe T-cell mediated toxicities that limit the widespread implementation of the therapy. To address these challenges, we engineered and systematically optimized bispecific BCMA/CS1 CAR-T cells that recognize tumor cells if the target expresses either BCMA or CS1, thus effectively preventing antigen escape for multiple myeloma. Furthermore, we engineered self-regulating CD19 CAR-T cells that secrete cytokine modulators, which can neutralize inflammatory cytokines at the site of activated T cells, to effectively prevent cytokine release syndrome intrinsically and promptly. Taken together, we ultimately seek to improve the efficacy and safety of CAR-based adoptive-T cell therapy to broaden the application of the therapy and provide effective cancer treatment.