The fourth-generation CAR-T cell therapy refers to the second-generation CAR-T cells armed with immune stimulatory cytokines (e.g., IL-12, IL-15, and IL-18) that are released while they engage targeted tumor cells, leading to the improvement of CAR-T cell expansion/persistence as well as the promotion of the antigen spreading by recruiting endogenous T cells or NK cells (11–16). This evidence concerns the gene IL15 and neoplasm.