B-cell maturation antigen (BCMA) and B-lymphocyte antigen CD19 (CD19) (BCMA and CD19)

B-cell maturation antigen (BCMA) and B-lymphocyte antigen CD19 are two critical cell surface proteins used as co-targets in the treatment of B-cell malignancies, particularly multiple myeloma and certain lymphomas (UniProt Q02223, P15391). BCMA is a member of the tumor necrosis factor receptor superfamily that is highly expressed on malignant plasma cells and is essential for their survival, while CD19 is a pan-B-cell marker involved in B-cell receptor signaling (PubMed: 32690327). By targeting both antigens simultaneously, therapeutic agents like dual-specific Chimeric Antigen Receptor (CAR) T-cells aim to overcome the challenge of antigen escape, a common mechanism of resistance where tumor cells downregulate a single target to evade the immune system (Nature Reviews Clinical Oncology, 2019). This dual-targeting approach enhances the depth and durability of clinical responses by ensuring that even progenitor or sub-populations of cancer cells lacking one of the markers are effectively eliminated. Clinical applications primarily focus on relapsed or refractory multiple myeloma, where BCMA is the primary target and CD19 is often expressed on a subset of myeloma stem cells (Blood, 2021).

Other names

TNFRSF17CD269B-cell maturation factorB-lymphocyte surface antigen B4CVID3CD19 molecule

Simultaneous binding of BCMA and CD19 by engineered T-cells (CAR-T) or bispecific antibodies to induce T-cell mediated lysis of malignant B-cells and plasma cells, reducing the risk of relapse due to antigen escape.