These mainly include the following: (1) extracellular PD-1 fused to the intracellular CD28-activating domain, thus transforming PDL1—PD1 binding into an activating signal and increasing anti-tumor efficacy; (2) secretion of the PD-1 Fc fusion protein by CAR-T cells, which then binds to PD-L1, preventing its suppressive effects on T cells; (3) downregulation of inhibitory checkpoint molecules, such as the PD1 and ITIM (immunoreceptor tyrosine-based inhibitory motif) domains (TIGIT) or Hematopoietic Progenitor Kinase 1 (HPK1) [177]. The gene discussed is CD28; the disease is neoplasm.