CXCR4-modified anti-BCMA CAR T cells

A preparation of T lymphocytes that have been genetically engineered to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; TNFRSF17) with modification of the C-X-C chemokine receptor type 4 (CXCR4), with potential immunomodulating and antineoplastic activities. Upon administration, the CXCR4-modified anti-BCMA CAR T cells target and bind to tumor cells expressing BCMA and induce selective cytotoxicity in those tumor cells. The modification of the stromal-cell derived factor-1 (SDF-1 or CXCL12) receptor CXCR4 may improve the penetration of CAR T cells into the tumor microenvironment (TME). 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.