期刊
CELL CHEMICAL BIOLOGY
卷 28, 期 1, 页码 60-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2020.10.004
关键词
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资金
- National Natural Science Foundation of China [81788101, 81630044, 81803419, 91753202, 21778015, 81821004]
- National Key Research and Development Program of China [2019ZX09739]
- Chinese Academy of Medical Science Innovation Fund for Medical Sciences [CIFMS 2017-12M-1-008,2016-12M-1-003]
- PUMC Youth Fund [2017350001]
This study demonstrates a photoswitchable approach to regulate CAR-T cells, allowing rapid termination of cytotoxicity without compromising tumor therapy.
Chimeric antigen receptor (CAR)-T-based therapeutics are a breakthrough in cancer treatment; however, they are hampered by constitutive activation, which leads to worrisome side effects. Engineering CAR-T cells to be as tightly controllable as possible remains a topic of ongoing investigation. Here, we report a photoswitchable approach that uses a mediator for the at-will regulation of CAR-T cells. This mediator carries dual folate and fluorescein isothiocyanate moieties tethered by an ortho-nitrobenzyl ester photocleavable linker. CAR-T cells were shown to be highly cytotoxic to targeted cells only in the presence of the mediator and acted in a dose-dependent manner. The toxicity of CAR-T cells can be rapidly terminated by cleavage of the mediator, and the effects of CAR-T cells can be activated again by resupplementation with the mediator without compromising tumor therapy. The approach described here provides a direction for enhancing the controllability of CAR-T cells and can likely be applied in other immunotherapies.
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