Meanwhile, to reduce toxicity and enhance the safety of CAR T-cell therapy targeting leukemia-associated target antigens such as CD33 or CD123 and preventing/predicting on-target/off-tumor effects an appropriate target antigen selection and validation remain critical steps in the development of AML CAR T-cell therapy and that can be integrated within the control of CAR activity by suicide genes or switch-off designs, optimization of CAR construct designs and/or combination approaches. The gene discussed is CD33; the disease is neoplasm.