allogeneic iPSC-derived anti-CD19-CAR/IL-15-expressing NK cells CNTY-101

A preparation of allogeneic natural killer (NK) cells derived from a clonal master induced pluripotent stem cell (iPSC) line, and engineered to express a chimeric antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv) derived from the anti-CD19 monoclonal antibody FMC63 and coupled to the CD28 and zeta chain of the TCR/CD3 complex (CD3-zeta) costimulatory signaling domains, and interleukin 15 (IL-15), with potential immunostimulatory and antineoplastic activities. Upon administration, allogeneic iPSC-derived anti-CD19-CAR/IL-15-expressing NK cells CNTY-101 recognize, bind to and induce selective cytotoxicity in CD19-expressing tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and potentiates the immune response against tumor cells. The human tumor associated antigen (TAA) CD19 is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. CNTY-101 is also engineered with a safety switch composed of a shorter version of the extracellular domain of human epidermal growth factor receptor (EGFR). This allows the elimination of CNTY-101 upon the administration of anti-EGFR antibodies such as cetuximab. In addition, CNTY-101 is gene-edited to prevent its elimination by the patient’s NK cells, CD4 and CD8 T cells.