G protein-coupled receptor class C group 5 member D and Cluster of differentiation 3 complex (GPRC5D–CD3)

The GPRC5D–CD3 immune synapse is a therapeutic target complex formed by the simultaneous engagement of G protein-coupled receptor class C group 5 member D (GPRC5D) on malignant plasma cells and the Cluster of differentiation 3 (CD3) epsilon subunit on T-lymphocytes. GPRC5D is an orphan receptor that is highly and specifically overexpressed on the surface of multiple myeloma cells, with limited expression in normal tissues such as the skin and keratinized structures. CD3 is a critical co-receptor involved in activating both cytotoxic T-cells and T-helper cells. By bridging these two molecules using bispecific antibodies or T-cell engagers, the therapy bypasses the need for major histocompatibility complex (MHC) class I recognition, forcing the formation of a stable immune synapse. This interaction leads to the localized release of cytotoxic granules and cytokines, resulting in the targeted destruction of myeloma cells. This approach has emerged as a highly effective strategy for treating relapsed or refractory multiple myeloma, particularly in patients who have exhausted other lines of therapy such as BCMA-targeted agents.

Other names

GPRC5D x CD3GPRC5D/CD3 bispecific targetGPRC5D-CD3 T-cell engager target

Bispecific antibody-mediated redirection of T-cells to GPRC5D-expressing malignant plasma cells, inducing the formation of an artificial immune synapse that triggers T-cell activation, degranulation, and subsequent perforin/granzyme-mediated lysis of the tumor cell.