To target NK cells to cancer cells that express the disialoganglioside GD2 as a tumor-associated surface antigen, we generated a codon-optimized and fully humanized chimeric antigen receptor (CAR hu14.18.28.z), which harbors an immunoglobulin heavy-chain signal peptide and a single-chain fragment variable (scFv) domain derived from humanized GD2-specific antibody hu14.18 [36], linked to intracellular CD28 and CD3ζ signaling domains via a Myc-tag, an optimized CD8α hinge region, and the CD28 transmembrane domain. Here, CD28 is linked to cancer.