anti-BCMA CAR T-cell therapy + anti-BCMA bispecific T-cell engager

Anti-BCMA CAR T-cell therapy + anti-BCMA bispecific T-cell engager is a combination immunotherapy approach in which a B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell product is used together with a BCMA-targeted bispecific T-cell engager antibody to treat multiple myeloma and other BCMA-expressing plasma cell malignancies. BCMA is a TNFR superfamily receptor selectively expressed on normal and malignant plasma cells and late-stage B cells, making it an attractive target for myeloma-directed immunotherapies.[2] Anti-BCMA CAR T cells are autologous T lymphocytes genetically modified ex vivo to express a CAR incorporating an anti-BCMA binding domain (often a single-chain antibody fragment), a costimulatory domain such as 4-1BB or CD28, and a CD3ζ signaling domain; after reinfusion, these cells recognize and lyse BCMA-positive myeloma cells independent of MHC, expand in vivo, and can induce deep and durable remissions in relapsed or refractory multiple myeloma.[2][3] Anti-BCMA bispecific T-cell engagers are recombinant antibodies that simultaneously bind BCMA on myeloma cells and CD3 on T cells, promoting formation of an immunologic synapse and redirecting polyclonal T cells to kill BCMA-expressing tumor cells, including in patients who have relapsed after prior therapies. This conceptual combination is being explored as a strategy to enhance depth and duration of response, overcome mechanisms of resistance such as antigen downregulation or T-cell exhaustion after BCMA CAR T administration, and provide sequential or overlapping BCMA-directed immune pressure, although specific fixed-dose combination products and standardized regimens are still under clinical investigation.[2][6]