trispecific CAR-T therapy targeting BCMA, GPRC5D, and CD38

This trispecific CAR-T cell therapy is designed to target three distinct antigens highly expressed on malignant plasma cells in relapsed/refractory multiple myeloma (R/RMM): B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D), and Cluster of differentiation 38 (CD38). The therapy integrates a novel JAK/STAT5 signaling pathway to enhance CAR-T cell fitness, promote expansion, and improve antitumor efficacy, particularly in the presence of soluble BCMA, while minimizing antigen escape and avoiding toxicity to CD38-positive normal cells. Preclinical studies have shown robust anti-tumor activity, leading to complete tumor eradication and prolonged survival in models of antigen-heterogeneous MM.