Allogeneic CRISPR-edited Anti-BCMA CAR-T Cells CB-011
allogeneic crispr-edited anti-bcma car-t cells cb-011
"A preparation of allogeneic, off-the-shelf T-lymphocytes genetically modified and clustered regularly interspaced short palindromic repeats (CRISPR)-edited to contain a deletion of the TRAC gene, a site-specific insertion of 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) into the TRAC gene, a deletion of the B2M gene, and a site-specific insertion of a gene encoding a B2M-HLA-E-peptide fusion into the B2M gene, with potential immunostimulating and antineoplastic activities. Upon administration, the allogeneic CRISPR-edited anti-BCMA CAR-T cells CB-011 recognize and bind to BCMA-expressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of BCMA-positive tumor cells. Knock out of the TRAC gene eliminates the endogenous T-cell receptors (TCRs), thereby preventing graft-versus-host disease (GvHD). The B2M protein is removed to eliminate endogenous HLA class I expression on the surface of the CB-011 CAR-T cells, which protects the CAR-T cells from host T-cell rejection. The B2M-HLA-E fusion protein is inserted to protect the CAR-T cells from host natural killer (NK) cell rejection. 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."