BCMA-TGF-beta insensitive armored CAR T cells

A preparation of human T lymphocytes genetically engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) and armored to be insensitive to the immunosuppressive cytokine transforming growth factor-beta (TGF-beta), with potential immunostimulating and antineoplastic activities. Upon administration, BCMA-TGF-beta insensitive armored CAR T cells specifically recognize and induce selective toxicity in BCMA-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, found on the surfaces of plasma cells and overexpressed on malignant plasma cells, plays a key role in plasma cell proliferation and survival. Though the nature of the TGF-beta armor has yet to be fully elucidated, it prevents the binding of TGF-beta to the CAR T-cells. TGF-beta negatively regulates T-cell proliferation and activation, contributes to the immunosuppressive nature of the tumor microenvironment (TME), and plays a key role in promoting tumor initiation, metastasis, and suppressing anti-tumor immunity.