GPRC5D x BCMA x CD3

Class

Trispecific antibody (T-cell engager)

Pathway

T-cell redirection against myeloma cells co-expressing GPRC5D and/or BCMA — dual-tumor-antigen binding designed to reduce antigen-escape relapse compared with single-target bispecifics

GPRC5D and BCMA are two proteins commonly found on the surface of malignant plasma cells in multiple myeloma, a cancer arising from antibody-producing cells in the bone marrow. BCMA (B-cell maturation antigen) normally supports plasma cell survival, while GPRC5D is a poorly understood receptor whose expression outside tumors is largely limited to hair follicles, making it a fairly tumor-selective marker. CD3 is a signaling protein present on essentially all T cells, the immune system's cytotoxic effector cells. A trispecific antibody built around this combination acts as a T-cell engager: one binding arm grips CD3 to recruit a patient's own T cells, while two other arms independently recognize BCMA and GPRC5D on myeloma cells. This physically bridges T cell and tumor cell, forcing formation of an immune synapse that triggers T-cell-mediated killing without relying on the tumor's own antigen-presentation machinery. The rationale for engaging two tumor antigens rather than one is to counter antigen escape, a resistance pattern in which tumor cells that lose or reduce one target survive treatment directed at that target alone. Requiring loss of both antigens for escape is intended to produce more durable disease control in myeloma, particularly disease that has relapsed after earlier therapies.