allogeneic iC9/CD19-CAR-CD28-zeta-2A-IL15-transduced cord blood-derived natural killer cells TAK-007

A preparation of allogeneic, umbilical cord blood (CB)-derived natural killer cells (NKs) transduced with a retroviral vector expressing interleukin-15 (IL-15) and encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD19 that is coupled to the co-stimulatory domains of CD28 and to the zeta chain of the TCR/CD3 complex (CD3-zeta), and is linked to the suicide gene inducible caspase 9 (iCasp9; iC9), with potential immunomodulating and antineoplastic activities. Upon transfusion, the allogeneic iC9/CD19-CAR-CD28-zeta-2A-IL15-transduced CB-NKs TAK-007 recognize, bind to and induce selective cytotoxicity in CD19-expressing tumor cells. The iCasp9 safety switch consists of a full-length caspase 9, including its caspase recruitment domain, linked to a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V). If the administered NK cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered; AP1903 binds to the FKBP12-F36V drug-binding domain, activates caspase 9, and results in apoptosis of the administered NK cells. CD19 antigen is a B-cell-specific cell surface antigen expressed in all B-cell lineage malignancies. IL-15 enhances the cytotoxic effect of the NK cells.