CD28 and neoplasm: Studies have shown that optimizing the CD28-based CAR structure—through approaches such as mutating the CD28 signaling motif, combining it with other co-stimulatory molecules, and modifying its upstream and downstream structures—is expected to improve the durability and anti-tumor efficacy of CAR-T cells by enhancing their ability to regulate T cell proliferation and survival, with a relatively optimistic safety profile (Figure 5, Table 2).