Furthermore, mutation design on CD28 costimulatory domain of second-generation CAR T-cells is another strategy that not only improved CAR T-cell durability and decreased exhaustion, but also may be reduced expression of programmed cell death protein 1 (PD-1) in B-cell acute lymphoblastic leukemia (B-ALL) mice [160]. The gene discussed is PDCD1; the disease is precursor B-cell acute lymphoblastic leukemia.