Titratable control of engineered therapeutic T cells through an ON-switch chimeric antigen receptor. Titratable control of engineered therapeutic T cells.

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Titratable control of engineered therapeutic T cells through an ON-switch chimeric antigen receptor. Titratable control of engineered therapeutic T cells through an ON-switch chimeric antigen receptor. A conventional CAR design activates T cells upon target cell engagement but can yield severe toxicity due to excessive immune response. The ON-switch CAR design, which has a split architecture, requires a priming small molecule, in addition to the cognate antigen, to trigger therapeutic functions. The magnitude of responses such as target cell killing can be titrated by varying the dosage of small molecule to mitigate toxicity. scFv, single-chain variable fragment; ITAM, immunoreceptor tyrosine-based activation motif. Chia-Yung Wu et al. Science 2015;350:aab4077 Published by AAAS