Single cell Dissection of Resistance to anti-BCMA CAR-T cell Therapy

Despite advances in therapy, multiple myeloma remains incurable in most patients. Immunotherapies may possess unique mechanism(s) of action to overcome drug resistance, potentially providing long-term tumor surveillance and durable disease control. Anti-B-cell maturation antigen (BCMA) CAR-T cell therapy has recently emerged, with dramatic clinical responses seen. Nevertheless, primary and acquired resistance is observed with the current generation of anti-BCMA CAR-T cells. The mechanisms that govern the expansion, persistence, and effector function of these cells are unknown. Further, the interaction of CARs with the myeloma bone marrow (BM) microenvironment remains uncharted, which hampers the ability to modulate the immune response to an optimal safe and efficacious zone. We utilized single-cell approaches to identify mechanisms of resistance to CAR-T cells.