Both NKp30-CD28 CAR TCRKO and NKp30-CD137 CAR TCRKO CAR T cells exerted potent anti-tumoral responses to AML and the melanoma cell line A375 in vitro, while NKp30-CD28 CAR TCRKO T cells elicited superior responses and sustained tumor burden control in vivo in a preclinical NSG xenograft tumor model. The gene discussed is CD28; the disease is melanoma.