First-generation CARs composed of the CD3ζ chain [40, 41] and second-generation CARs composed of CD28 and CD3ζ [38, 42–44], 4-1BB and CD28 [45], 4-1BB and CD3ζ [46, 47], 4-1BB, CD28 and CD3ζ [48], or CD137 and CD3ζ [49, 50] were applied to redirect NK cells against tumor cells. This evidence concerns the gene CD28 and neoplasm.