GPRC5D-directed CAR T cells

GPRC5D-directed CAR T cells are autologous chimeric antigen receptor (CAR) T-cell therapies engineered to express synthetic receptors that recognize and target the G protein-coupled receptor, class C, group 5, member D (GPRC5D) antigen. GPRC5D is highly expressed on malignant plasma cells in multiple myeloma with limited expression on normal tissues, primarily keratinized cells (such as in nail beds and skin), making it an ideal target for immunotherapy in relapsed/refractory multiple myeloma (RRMM)[1][3][4][6]. The CAR construct typically includes a single-chain variable fragment (scFv) specific for GPRC5D, a costimulatory domain (usually 4-1BB or CD28), and a CD3ζ signaling domain[1][5]. These products are custom-developed for each patient from autologous T cells, which are isolated by leukapheresis, genetically modified using viral vectors, expanded ex vivo, and infused back into the patient[2]. Multiple variants (e.g., MCARH109, BMS-986393/Arlocabtagene autoleucel, OriCAR-017, CC-95266) are in clinical development, often in patients previously treated with anti-BCMA therapies[3][4][6]. In phase 1 studies, these therapies have shown high overall response rates (70% or higher), including complete responses and MRD negativity, and promising safety profiles, particularly in heavily pretreated RRMM[3][4][5][6]. No GPRC5D-directed CAR T cell therapy is yet commercially approved for any indication as of August 2025[5].

Other names

G protein-coupled receptor class C group 5 member D-directed CAR T cellsanti-GPRC5D CAR T cellsanti-GPRC-5D CAR T cellsanti-GPRC 5D CAR T cellsGPRC5D-targeted CAR T cellsGPRC-5D-targeted CAR T cellsGPRC 5D-targeted CAR T cells