GPRC5D x CD3

Class

Bispecific antibody (T-cell engager)

Pathway

T-cell redirection — cross-links GPRC5D on myeloma cells with CD3 on T cells to trigger T-cell-mediated cytotoxicity

GPRC5D is an orphan cell-surface receptor belonging to the G-protein-coupled receptor family. Its expression is largely restricted to malignant plasma cells in multiple myeloma and to keratinized tissues such as hair follicles and, to some extent, skin and nail structures, with minimal presence on other normal cell types. This restricted distribution makes it an attractive target for redirecting immune attack against myeloma cells while limiting exposure elsewhere in the body. A GPRC5D x CD3 bispecific antibody is engineered to bind simultaneously to GPRC5D on tumor cells and to CD3, a component of the T-cell receptor complex on cytotoxic T lymphocytes. This dual binding physically bridges a T cell to a tumor cell, forming an artificial immunological synapse that activates the T cell independently of its native antigen-recognition machinery. Activated T cells then release cytotoxic granules containing perforin and granzymes, killing the myeloma cell directly. This approach broadens the immunotherapeutic toolkit for multiple myeloma beyond BCMA-directed agents, offering an alternative or complementary antigen target that may remain effective if BCMA expression is lost or downregulated during disease progression.