G protein–coupled receptor class C group 5 member D (GPRC5D) and T cell surface glycoprotein CD3 (GPRC5D (for receptor); CD3 (for T cell co-receptor))

G protein–coupled receptor class C group 5 member D (GPRC5D) is an orphan, seven-pass transmembrane receptor highly expressed on malignant plasma cells in multiple myeloma, making it a promising surface antigen for immunotherapy. CD3 is a multi-subunit co-receptor present on all T cells and is essential for T cell activation. In the context of innovative therapies for multiple myeloma, GPRC5D and CD3 are paired as targets in bispecific antibodies and T cell–redirecting agents, enabling the recruitment of T cells to directly kill myeloma cells while sparing other tissues. These therapies are currently in clinical development and have shown robust efficacy in treatment-resistant multiple myeloma, though they carry risks related to immune activation and off-tumor toxicities.

Other names

GPRC5D and CD3 (therapeutic concept)GPRC5D and CD3 (target pair)GPRC5D×CD3 bispecificG protein–coupled receptor family C group 5 member DT cell surface glycoprotein CD3CD3 complex (includes CD3ε, CD3γ, CD3δ, CD3ζ subunits)

T cell–redirecting: Bispecific antibody binds GPRC5D on tumor cells and CD3 on T cells, inducing proximity-driven T cell activation and killing of GPRC5D-positive multiple myeloma cells. CAR-T: Engineered T cells with anti-GPRC5D specificity directly recognize and destroy GPRC5D-expressing cells.