B-cell maturation antigen and G protein-coupled receptor class C group 5 member D (BCMA x GPRC5D)

BCMA x GPRC5D represents a dual-antigen targeting strategy primarily utilized in the treatment of multiple myeloma. B-cell maturation antigen (BCMA) is a member of the TNF receptor superfamily essential for the survival of long-lived plasma cells, while G protein-coupled receptor class C group 5 member D (GPRC5D) is an orphan receptor highly and specifically expressed on malignant plasma cells and in heavily keratinized tissues. By targeting both molecules simultaneously, therapeutic agents aim to overcome the common clinical challenge of antigen escape, where tumor cells downregulate a single target to evade immune detection. This approach is currently being explored through bispecific T-cell engagers and chimeric antigen receptor (CAR) T-cell therapies to provide deeper and more durable responses in patients with relapsed or refractory disease. Clinical data suggest that this dual-targeting can maintain efficacy even in patients who have previously failed single-target BCMA therapies.

Other names

Tumor necrosis factor receptor superfamily member 17 (TNFRSF17)CD269G-protein coupled receptor family C group 5 member DBCMA/GPRC5D dual target

Dual-targeting agents such as bispecific antibodies or multi-specific CAR-T cells simultaneously bind to BCMA and GPRC5D on the surface of malignant plasma cells. This dual engagement facilitates the recruitment and activation of T cells to induce tumor cell lysis, while reducing the risk of immune escape through antigen loss or downregulation of a single target.