Ramantamig: A novel BCMA×GPRC5D×CD3 trispecific antibody

Results from a preclinical study, evaluating ramantamig, a novel T‑cell-engaging trispecific antibody (TsAb) targeting B‑cell maturation antigen (BCMA), G‑protein-coupled receptor family C group 5 member D (GPRC5D), and cluster of differentiation 3 (CD3), in multiple myeloma (MM) models, were published in Blood by Pillarisetti et al. The study assessed binding specificity and T‑cell-mediated cytotoxicity across MM cell lines, whole blood cocultures, bone marrow mononuclear cell samples, and xenograft models.

Key data:In BCMA/GPRC5D dual-positive cell lines, ramantamig demonstrated T‑cell-mediated cytotoxicity with 50% effective concentration (EC50) values of 0.002–0.312 nM for cytotoxicity and 0.008–1.070 nM for T‑cell activation, with no activity in target-negative cells. In gene knockout models, cytotoxicity EC50 values were 0.007 nM in wild-type cells, 0.330 nM in GPRC5D-knockout cells, and 4.789 nM in BCMA-knockout cells, supporting enhanced avidity with dual-target binding. In whole blood assays, mean EC50 values were 0.274 nM for cytotoxicity and 0.376 nM for T‑cell activation. Ramantamig also induced dose-dependent depletion of CD138+ plasma cells in bone marrow samples from patients with MM (N = 4), and demonstrated antitumor activity in xenograft models.

Key learning: Dual BCMA and GPRC5D targeting with ramantamig may enhance T‑cell-mediated cytotoxicity and help address tumor heterogeneity and antigen escape in MM.