allogeneic anti-BCMA CAR T cells ALLO-605

A preparation of allogeneic, transcription activator-like effector nuclease (TALEN)-engineered, gene-edited T-lymphocytes that have been transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) targeting the human tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) and engineered to express a constitutively active chimeric cytokine receptor (CACCR), with potential immunostimulating and antineoplastic activities. Using TALEN technology, the T-cell receptor (TCR) alpha chain (TRAC) and CD52 genes are inactivated. Upon administration, the allogeneic anti-BCMA CAR T Cells ALLO-605 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 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. Inactivation of the CD52 gene makes the modified donor T-cells resistant to an anti-CD52 monoclonal antibody treatment, that is used during lymphodepletion. The knockout of TRAC eliminates TCR expression and is intended to abrogate the potential induction of graft-versus-host disease (GvHD) by the donor T-cells. The expression of CACCR allows for intracellular cytokine activation signaling, which may enhance expansion and persistence of the CAR T cells, thereby improving long-term anti-tumor activity. In addition, the incorporated CD20-based off-switch of ALLO-605 permits selective depletion of the ALLO-605 cells when the anti-CD20 monoclonal antibody rituximab is administered. ALLO-605 can also be inactivated with dasatinib.