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Current and future perspectives of chimeric antigen receptors against glioblastoma

Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological...

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Autores principales: Zhang, Josephine, Siller-Farfán, Jesús A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585667/
https://www.ncbi.nlm.nih.gov/pubmed/36284838
http://dx.doi.org/10.1093/immadv/ltac014
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author Zhang, Josephine
Siller-Farfán, Jesús A
author_facet Zhang, Josephine
Siller-Farfán, Jesús A
author_sort Zhang, Josephine
collection PubMed
description Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological malignancies, namely leukemia and multiple myeloma. However, CAR T cell therapy against solid tumors, and more specifically GBM, is still riddled with challenges preventing its widespread adoption. Here, we first establish the obstacles in ACT against GBM, including on-target/off-tumor toxicity, antigen modulation, tumor heterogeneity, and the immunosuppressive tumor microenvironment. We then present recent preclinical and clinical studies targeting well-characterized GBM antigens, which include the interleukin-13 receptor α2 and the epidermal growth factor receptor. Afterward, we turn our attention to alternative targets in GBM, including less-explored antigens such as B7-H3 (CD276), carbonic anhydrase IX, and the GD2 ganglioside. We also discuss additional target ligands, namely CD70, and natural killer group 2 member D ligands. Finally, we present the possibilities afforded by novel CAR architectures. In particular, we examine the use of armored CARs to improve the survival and proliferation of CAR T cells. We conclude by discussing the advantages of tandem and synNotch CARs when targeting multiple GBM antigens.
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spelling pubmed-95856672022-10-24 Current and future perspectives of chimeric antigen receptors against glioblastoma Zhang, Josephine Siller-Farfán, Jesús A Immunother Adv Review Glioblastoma multiforme (GBM) is the most malignant form of cancer in the central nervous system; even with treatment, it has a 5-year survival rate of 7.2%. The adoptive cell transfer (ACT) of T cells expressing chimeric antigen receptors (CARs) has shown a remarkable success against hematological malignancies, namely leukemia and multiple myeloma. However, CAR T cell therapy against solid tumors, and more specifically GBM, is still riddled with challenges preventing its widespread adoption. Here, we first establish the obstacles in ACT against GBM, including on-target/off-tumor toxicity, antigen modulation, tumor heterogeneity, and the immunosuppressive tumor microenvironment. We then present recent preclinical and clinical studies targeting well-characterized GBM antigens, which include the interleukin-13 receptor α2 and the epidermal growth factor receptor. Afterward, we turn our attention to alternative targets in GBM, including less-explored antigens such as B7-H3 (CD276), carbonic anhydrase IX, and the GD2 ganglioside. We also discuss additional target ligands, namely CD70, and natural killer group 2 member D ligands. Finally, we present the possibilities afforded by novel CAR architectures. In particular, we examine the use of armored CARs to improve the survival and proliferation of CAR T cells. We conclude by discussing the advantages of tandem and synNotch CARs when targeting multiple GBM antigens. Oxford University Press 2022-06-01 /pmc/articles/PMC9585667/ /pubmed/36284838 http://dx.doi.org/10.1093/immadv/ltac014 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Zhang, Josephine
Siller-Farfán, Jesús A
Current and future perspectives of chimeric antigen receptors against glioblastoma
title Current and future perspectives of chimeric antigen receptors against glioblastoma
title_full Current and future perspectives of chimeric antigen receptors against glioblastoma
title_fullStr Current and future perspectives of chimeric antigen receptors against glioblastoma
title_full_unstemmed Current and future perspectives of chimeric antigen receptors against glioblastoma
title_short Current and future perspectives of chimeric antigen receptors against glioblastoma
title_sort current and future perspectives of chimeric antigen receptors against glioblastoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585667/
https://www.ncbi.nlm.nih.gov/pubmed/36284838
http://dx.doi.org/10.1093/immadv/ltac014
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