First-in-human proof-of-concept for a rapidly switchable UniCAR targeting CD123 for treatment of AML. (A) Schematic presentation of the UniCAR platform. Autologous T cells are genetically engineered to express UniCAR, which does not recognize a surface protein, and hence, UniCAR-T are inactive under physiologic conditions. A soluble adapter consisting of the UniCAR epitope (UCE) linked to a single-chain fragment variable directed against CD123 (TM123) is required for antigen-specific redirection and activation of UniCAR-T. (B) Rapid recovery of leukocytes (WBC), neutrophils, and platelets in 3 treated AML patients after stop of TM123 infusion. Asterisks indicate timing of platelet transfusions. (C) UniCAR-T-cell numbers in peripheral blood (PB) over the course of treatment. Cell number was calculated from vector copy number determined by digital droplet polymerase chain reaction, mean and standard deviation are shown.