CD274 and neoplasm: For instance, CAR-T cells against carbonic anhydrase (an enzyme that is overexpressed in many hypoxic solid tumors) were engineered to secrete anti-PD-L1 antibodies, and these modified CAR-T cells showed lower expression of exhaustion molecules (PD-1, TIM-3, and LAG3) after contact with tumor cells, compared to the conventional anti-carbonic anhydrase CAR-T cells.