CAR-T directly targets cancer cells via CAR, which consists of a cancer antigen-specific external single-chain variable fragment (scFv), a transmembrane domain, an intracellular signaling domain, and a costimulatory domain from receptors (e.g., CD28, OX40, CD137), while TCR-T recognizes intracellular specific antigens presented by major histocompatibility complex (MHC) molecules of cancer cells through the transduced natural TCR (α- and β-chains non-covalently linked to the CD3 complex on the surface), which leads to the activation of T cells and destruction of cancer cells [39,40]. This evidence concerns the gene CD28 and cancer.