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Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encounte...

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Autores principales: Andrea, Alain E., Chiron, Andrada, Mallah, Sarah, Bessoles, Stéphanie, Sarrabayrouse, Guillaume, Hacein-Bey-Abina, Salima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861853/
https://www.ncbi.nlm.nih.gov/pubmed/35211124
http://dx.doi.org/10.3389/fimmu.2022.830292
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author Andrea, Alain E.
Chiron, Andrada
Mallah, Sarah
Bessoles, Stéphanie
Sarrabayrouse, Guillaume
Hacein-Bey-Abina, Salima
author_facet Andrea, Alain E.
Chiron, Andrada
Mallah, Sarah
Bessoles, Stéphanie
Sarrabayrouse, Guillaume
Hacein-Bey-Abina, Salima
author_sort Andrea, Alain E.
collection PubMed
description During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encountered by CAR-T cells in solid malignancies is the immunosuppressive tumor microenvironment (TME). The TME impedes tumor trafficking and penetration of T lymphocytes and installs an immunosuppressive milieu by producing suppressive soluble factors and by overexpressing negative immune checkpoints. In order to overcome these hurdles, new CAR-T cells engineering strategies were designed, to potentiate tumor recognition and infiltration and anti-cancer activity in the hostile TME. In this review, we provide an overview of the major mechanisms used by tumor cells to evade immune defenses and we critically expose the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors.
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spelling pubmed-88618532022-02-23 Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment Andrea, Alain E. Chiron, Andrada Mallah, Sarah Bessoles, Stéphanie Sarrabayrouse, Guillaume Hacein-Bey-Abina, Salima Front Immunol Immunology During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encountered by CAR-T cells in solid malignancies is the immunosuppressive tumor microenvironment (TME). The TME impedes tumor trafficking and penetration of T lymphocytes and installs an immunosuppressive milieu by producing suppressive soluble factors and by overexpressing negative immune checkpoints. In order to overcome these hurdles, new CAR-T cells engineering strategies were designed, to potentiate tumor recognition and infiltration and anti-cancer activity in the hostile TME. In this review, we provide an overview of the major mechanisms used by tumor cells to evade immune defenses and we critically expose the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors. Frontiers Media S.A. 2022-02-08 /pmc/articles/PMC8861853/ /pubmed/35211124 http://dx.doi.org/10.3389/fimmu.2022.830292 Text en Copyright © 2022 Andrea, Chiron, Mallah, Bessoles, Sarrabayrouse and Hacein-Bey-Abina 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
Andrea, Alain E.
Chiron, Andrada
Mallah, Sarah
Bessoles, Stéphanie
Sarrabayrouse, Guillaume
Hacein-Bey-Abina, Salima
Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
title Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
title_full Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
title_fullStr Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
title_full_unstemmed Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
title_short Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
title_sort advances in car-t cell genetic engineering strategies to overcome hurdles in solid tumors treatment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861853/
https://www.ncbi.nlm.nih.gov/pubmed/35211124
http://dx.doi.org/10.3389/fimmu.2022.830292
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