allogeneic CRISPR-edited anti-CD19 CAR T cells PACE CART19

An off-the-shelf (OTS) preparation of human allogeneic T lymphocytes transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv) and the co-stimulatory domain 4-1BB (CD137) coupled to the zeta chain of the T-cell receptor (TCR)/CD3 complex (CD3-zeta), and electroporated with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease complex to eliminate the expression of endogenous TCR, HLA class I and HLA class II molecules, with potential immunostimulating and antineoplastic activities. Upon administration, allogeneic CRISPR-edited anti-CD19 CAR T cells PACE CART19 recognize and bind to CD19-expressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of CD19-expressing tumor cells. The removal of endogenous TCR, HLA class I and HLA class II molecules prevents allogeneic immune responses and reduces the risk of graft-versus-host disease (GvHD). The tumor-associated antigen (TAA) CD19 is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies.