An oxygen sensitive self-decision making engineered CAR T-cell

Scientific Reports - Tập 7 Số 1
Alexandre Juillerat1, Alan Maréchal2, Jean Marie Filhol2, Yannick Valogne2, Julien Valton1, Aymeric Duclert2, Philippe Duchâteau2, Laurent Poirot2
1Cellectis Inc, 430E, 29th street, NYC, 10016, NY, USA
2Cellectis, 8 rue de la croix Jarry, 75013, Paris

Tóm tắt

AbstractA key to the success of chimeric antigen receptor (CAR) T-cell based therapies greatly rely on the capacity to identify and target antigens with expression restrained to tumor cells. Here we present a strategy to generate CAR T-cells that are only effective locally (tumor tissue), potentially also increasing the choice of targetable antigens. By fusing an oxygen sensitive subdomain of HIF1α to a CAR scaffold, we generated CAR T-cells that are responsive to a hypoxic environment, a hallmark of certain tumors. Along with the development of oxygen-sensitive CAR T-cells, this work also provides a basic framework to use a multi-chain CAR as a platform to create the next generation of smarter self-decision making CAR T-cells.

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