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Comment
. 2023 Oct 10;56(10):2180-2182.
doi: 10.1016/j.immuni.2023.09.006.

Releasing the brake: CTLA-4 loss turbocharges CAR T cells

Roland C Schelker  1 , Luca Gattinoni  2
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Releasing the brake: CTLA-4 loss turbocharges CAR T cells

Roland C Schelker et al. Immunity. .
Free article

Abstract

Immune checkpoint receptor-induced T cell dysfunction is a major cause of CAR T cell treatment failure. In this issue, Agarwal et al. report that CRISPR/Cas9 deletion of CTLA4, but not PDCD1 or CTLA4 and PDCD1, enhances CD28 signaling, restoring fitness and antitumor function of CAR T cells, including those derived from patients who failed CAR T cell therapy.

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Conflict of interest statement

Declaration of interests L.G. has consulting agreements with Lyell Immunopharma, is on the scientific advisory boards of Poseida Therapeutics and Kiromic, and is a stockholder of Poseida Therapeutics. The figure was created with BioRender.com.

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