allogeneic TCR-CD3 complex/CD16/IL-15-expressing natural killer cells

A preparation of allogeneic natural killer (NK) cells that have been engineered to express a T-cell receptor (TCR)-CD3 complex, CD16 Fc receptor, and interleukin 15 (IL-15), with potential immunostimulating and antineoplastic activities. Upon administration, allogeneic TCR-CD3 complex/CD16/IL-15-expressing NK cells lyse tumor cells. Upon coadministration with tumor-targeting and CD3-targeting bispecific antibodies, the tumor-targeting moiety binds to the tumor-associated antigens (TAAs) expressed on tumor cells and the anti-CD3 moiety binds to the TCR-CD3 complex expressed on the allogeneic NK cells. This may enhance NK cell-mediated lysis of the TAA-expressing tumor cells. Upon coadministration with certain tumor-targeting monoclonal antibodies, the Fab moiety of the antibodies binds to the TAAs expressed on tumor cells and the Fc moiety of the antibodies binds to CD16 expressed on the allogeneic NK cells. This leads to antibody-dependent cellular cytotoxicity (ADCC) of the antibody-bound tumor cells. 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. IL-15 promotes the survival of NK cells and enhances the cytotoxic effect of NK cells and activated anti-tumor T cells.