Decreasing the affinity of the PD-1 extracellular domain to PD-L1 aims to restrict the development of immune-related AEs due to on-target off-leukemia toxicity, meanwhile, the affinity to CD33 tumor antigen is still high, which aims to maintain high specificity for CD33 + PD-L1+ double-positive cells other than all PD-L1+ cells. The gene discussed is CD274; the disease is leukemia.