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


ABSTRACT: A 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 HIF1? 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.

SUBMITTER: Juillerat A 

PROVIDER: S-EPMC5247770 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Juillerat Alexandre A   Marechal Alan A   Filhol Jean Marie JM   Valogne Yannick Y   Valton Julien J   Duclert Aymeric A   Duchateau Philippe P   Poirot Laurent L  

Scientific reports 20170120


A 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 ce  ...[more]

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