Like T cells, which target the activating site CD16 on NK cells, as well as other tumor and NK cell sites, it is also possible to design Bi/Tri/Tetra-specific NK cell engagers (BiKEs, TriKEs, and TetraKEs) that elicit ISs between tumor cells and NK cells.473 BiKEs typically target one end to the CD16 single-chain variable fragment (scFv) on NK cells, while the other end targets specific antigens on tumor cells, such as EpCAM, CEA, EGFR, and HER2.474–477 These BiKEs can promote antigen-specific antibody-dependent cellular cytotoxicity (ADCC) but are unable to induce NK cell proliferation. This evidence concerns the gene EGFR and neoplasm.