CD28 and neoplasm: In the CAR, the TCR portion of T cells is replaced with antibody single-chain fragment specific toward a certain surface antigen of the tumor cell through non-viral or viral CAR vector and the cytoplasmic portion has a signaling component consisting of costimulatory domains such as CD28, 4-1BB, OX40, or CD40L and the CD3ζ signaling domain, depending on the different generations of the CAR T cells [154,158,159].