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- W3213927867 abstract "Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an off-switch by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule." @default.
- W3213927867 created "2021-11-22" @default.
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- W3213927867 date "2021-11-09" @default.
- W3213927867 modified "2023-10-18" @default.
- W3213927867 title "Tunable control of CAR T cell activity through tetracycline mediated disruption of protein–protein interaction" @default.
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- W3213927867 doi "https://doi.org/10.1038/s41598-021-01418-9" @default.
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