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CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells

Chimeric antigen receptors (CARs) in the canonical “second generation” format provide two signals for inducing T cell effector functions; the primary “signal-1” is provided through the TCR CD3ζ chain and the “signal-2” through a linked costimulatory domain to augment activation. While therapy with s...

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Detalles Bibliográficos
Autores principales: Thomas, Simone, Abken, Hinrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869021/
https://www.ncbi.nlm.nih.gov/pubmed/36700225
http://dx.doi.org/10.3389/fimmu.2022.1090959
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author Thomas, Simone
Abken, Hinrich
author_facet Thomas, Simone
Abken, Hinrich
author_sort Thomas, Simone
collection PubMed
description Chimeric antigen receptors (CARs) in the canonical “second generation” format provide two signals for inducing T cell effector functions; the primary “signal-1” is provided through the TCR CD3ζ chain and the “signal-2” through a linked costimulatory domain to augment activation. While therapy with second generation CAR T cells can induce remissions of leukemia/lymphoma in a spectacular fashion, CAR T cell persistence is frequently limited which is thought to be due to timely limited activation. Following the “three-signal” dogma for inducing a sustained T cell response, cytokines were supplemented to provide “signal-3” to CAR T cells. Recent progress in the understanding of structural biology and receptor signaling has allowed to engineer cytokines for more selective, fine-tuned stimulation of CAR T cells including an artificial autocrine loop of a transgenic cytokine, a cytokine anchored to the CAR T cell membrane or inserted into the extracellular CAR domain, and a cytokine receptor signaling moiety co-expressed with the CAR or inserted into the CAR endodomain. Here we discuss the recent strategies and options for engineering such “cytokine help intensified CAR” (CHIC) T cells for use in adoptive cell therapy.
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spelling pubmed-98690212023-01-24 CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells Thomas, Simone Abken, Hinrich Front Immunol Immunology Chimeric antigen receptors (CARs) in the canonical “second generation” format provide two signals for inducing T cell effector functions; the primary “signal-1” is provided through the TCR CD3ζ chain and the “signal-2” through a linked costimulatory domain to augment activation. While therapy with second generation CAR T cells can induce remissions of leukemia/lymphoma in a spectacular fashion, CAR T cell persistence is frequently limited which is thought to be due to timely limited activation. Following the “three-signal” dogma for inducing a sustained T cell response, cytokines were supplemented to provide “signal-3” to CAR T cells. Recent progress in the understanding of structural biology and receptor signaling has allowed to engineer cytokines for more selective, fine-tuned stimulation of CAR T cells including an artificial autocrine loop of a transgenic cytokine, a cytokine anchored to the CAR T cell membrane or inserted into the extracellular CAR domain, and a cytokine receptor signaling moiety co-expressed with the CAR or inserted into the CAR endodomain. Here we discuss the recent strategies and options for engineering such “cytokine help intensified CAR” (CHIC) T cells for use in adoptive cell therapy. Frontiers Media S.A. 2023-01-09 /pmc/articles/PMC9869021/ /pubmed/36700225 http://dx.doi.org/10.3389/fimmu.2022.1090959 Text en Copyright © 2023 Thomas and Abken https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Thomas, Simone
Abken, Hinrich
CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells
title CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells
title_full CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells
title_fullStr CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells
title_full_unstemmed CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells
title_short CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells
title_sort car t cell therapy becomes chic: “cytokine help intensified car” t cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869021/
https://www.ncbi.nlm.nih.gov/pubmed/36700225
http://dx.doi.org/10.3389/fimmu.2022.1090959
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