CD33 and neoplasm: To date, it has not been determined which co-stimulatory domain is the optimal in a CAR context for the treatment of AML, however, our studies demonstrate that CD33-targeting CARs utilizing a 4-1BB costimulatory domain performed well with regards to cytokine response (Figure 3), killing potency (Figure 4), persistence and the speed of tumor elimination in vitro (Figure 5), targeting domain specificity (Figure 6), HSCs toxicity profile (Figure 7), and tumor rejection and host survival in vivo (Figure 8).