CTLA4 and cancer: In cases where TCRs are ineffective owing to tumor antigen loss or downregulation, CRISPR is used to engineer T cells with enhanced specificity and affinity for tumor-associated antigens.489 Moreover, the CRISPR-Cas9 tool enables the knockout of known genes involved in T cell exhaustion, such as pdcd1 and ctla4.490–492 CAR and TCR T cells, engineered with disrupted checkpoint molecules, serve as powerful effector cells for combating infectious diseases and cancers.