Definition

An allogeneic, off-the-shelf, chimeric antigen receptor (CAR)-natural killer (NK) cell product derived from a clonal master induced pluripotent stem cell (iPSC) line, and engineered to express a NK cell-specific anti-CD19 CAR, a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, and a recombinant fusion of IL-15 and IL-15 receptor alpha (IL-15RF), with potential immunostimulatory and antineoplastic activities. Upon administration, iPSC-derived CD16/IL-15RF-expressing Anti-CD19 CAR-NK Cells FT596 recognize, bind to and induce selective cytotoxicity in CD19-expressing tumor cells. IL-15RF enhances the cytotoxic effect of the NK cells and the activated anti-tumor T-cells. When used in combination with monoclonal antibodies, the hnCD16 Fc receptor of FT596 binds to the Fc portion of tumor cell-bound monoclonal antibodies, leading to NK cell activation, cytokine secretion and enhanced antibody-dependent cellular cytotoxicity (ADCC). CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. CD16, also known as Fc-gamma receptor III, is normally expressed on the surface of NK cells, neutrophils, monocytes and macrophages, and plays a key role in initiating ADCC. It is often downregulated in certain cancers, thereby inhibiting the anti-tumor immune response.