BCMA CART cells secreting mutant PD-1Fc fusion protein

A preparation of T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; TNFRSF17) and secrete a fusion protein composed of programmed death 1 (PD-1; PDCD1; CD279; programmed cell death-1) and a human immunoglobulin Fc region, with potential immunomodulating and antineoplastic activities. Upon administration of the BCMA CAR T cells secreting mutant PD-1Fc fusion protein, these T cells target and bind to tumor cells expressing BCMA and induce selective cytotoxicity in those tumor cells. The expressed PD-1-Fc fusion protein targets and binds to programmed death ligand 1 (PD-L1; cluster of differentiation 274; CD274; programmed cell death-1 ligand 1) expressed on tumor cells, thereby halting PD-1/PD-L1-mediated signaling. This may decrease T-cell exhaustion and may enhance T-cell activity against the PD-L1-expressing tumor cells. BCMA, a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF). BCMA is found on the surfaces of plasma cells, is overexpressed on malignant plasma cells and plays a key role in plasma cell proliferation and survival. PD-1, an immune checkpoint receptor expressed on T cells, plays a key role in tumor immune evasion by binding to its ligand PD-L1 expressed on tumor cells.