For the activation of third generation CAR-T cells, specific antigens expressed on tumor cells bind to the extracellular CAR domain, a single-chain variable fragment (scFv), and then the signal is transmitted through the transmembrane linker to the intracellular signaling domains such as CD3ζ, CD28 and 4-1BB to induce CAR-T cell activation (24). Here, CD28 is linked to neoplasm.