Figure 1.

NK cells naturally target multiple antigens by binding the conserved crystallizable fragment (Fc) of IgG, unlike chimeric antigen receptor (CAR)–T cells or CAR–NK cells that are programmed to recognize a single antigen.A, NK cell Fc γ receptor IIIa/CD16a associates with either CD3ζ or the Fc ε receptor γ chain to activate an NK cell after ligation to an antibody-bound target (70, 71). The CAR-T example shown represents the tisagenlecleucel (Kymriah) therapy that targets CD19 on B-cell lymphoma. This CAR–NK construct likewise recently showed success (3, 72). Both CARs contain custom transmembrane and activation domains. B, Fc γ receptors bind to the crystallizable fragment of IgG. IgG, immunoglobulin G; NK, natural killer.