BCMA / GPRC5D

Class

Dual-target CAR-T cell therapy (autologous)

BCMA (B-cell maturation antigen) and GPRC5D are two proteins found on the surface of malignant plasma cells in multiple myeloma. BCMA is a receptor that supports plasma cell survival by binding growth factors from the tumor necrosis factor family, activating pro-survival signaling. GPRC5D is an orphan G-protein-coupled receptor whose normal function is not fully understood, but it is reliably expressed on myeloma cells and, notably, also on hair follicle cells. Chimeric antigen receptor (CAR) T-cell therapy re-engineers a patient's own T cells to recognize a chosen surface marker and destroy cells that display it. Single-target BCMA CAR-T therapies have shown that myeloma cells can survive treatment by reducing or losing BCMA expression, allowing relapse. A dual-target construct directing T cells against both BCMA and GPRC5D is designed to address this problem: because the two antigens are regulated independently, a tumor cell would need to lose both simultaneously to escape recognition, which is a much less likely event. This approach broadly matters in myeloma and other plasma cell disorders, where antigen heterogeneity and clonal evolution under treatment pressure are recurring drivers of relapse.