IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML

•Dual CAR strategy by low affinity interleukin-3–zetakine and CD33 costimulatory receptor minimizes on-target/off-tumor toxicity in CD123 and/or CD33 healthy cells.•Dual interleukin-3–zetakine /CD33 costimulatory-receptor cytokine-induced killer cells demonstrate high efficacy and specificity for CD123+/CD33+leukemic cells in preclinical models.