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Comment
. 2021 Jun 14;39(6):756-758.
doi: 10.1016/j.ccell.2021.05.011.

CAR T cells need a pitstop to win the race

Caitlin C Zebley  1 , Ben Youngblood  2
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Free article
Comment

CAR T cells need a pitstop to win the race

Caitlin C Zebley et al. Cancer Cell. .
Free article

Abstract

Prolonged TCR-driven stimulation can induce a dysfunctional T cell state, broadly described as T cell exhaustion, limiting the clinical potential of chimeric antigen receptor (CAR) T cells. Recent findings in Science indicate that early cessation of CAR T cell tonic signaling can prevent stabilization of exhaustion-associated epigenetic programs, enabling a prolonged anti-tumor response.

Keywords: CAR T cells; differentiation; effector; epigenetics; exhaustion; memory.

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Conflict of interest statement

Declaration of interests C.C.Z. and B.Y. have patents related to epigenetic programs serving as biomarkers of T cell exhaustion for T cell immunotherapies. They also have patents related to engineering approaches that modify the epigenome of T cells for enhancing immunotherapies. B.Y. has a consulting agreement with ElevateBio.

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  • Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling.
    Weber EW, Parker KR, Sotillo E, Lynn RC, Anbunathan H, Lattin J, Good Z, Belk JA, Daniel B, Klysz D, Malipatlolla M, Xu P, Bashti M, Heitzeneder S, Labanieh L, Vandris P, Majzner RG, Qi Y, Sandor K, Chen LC, Prabhu S, Gentles AJ, Wandless TJ, Satpathy AT, Chang HY, Mackall CL. Weber EW, et al. Science. 2021 Apr 2;372(6537):eaba1786. doi: 10.1126/science.aba1786. Science. 2021. PMID: 33795428 Free PMC article.

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