CD28 and neoplasm: Although many intracellular domains in costimulatory molecules can improve the tumor-killing activities of CAR-T cells, CD28 and 4-1BB intracellular domains are the most commonly used costimulatory domains, and CAR-T cells with either CD28 or the 4-1BB intracellular domain have shown dramatic antitumor capability and tolerable toxicity in clinical trials28,271,272,275.