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Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy engineers T-cells to express a synthetic receptor which redirects effector function to the tumor, to improve efficacy and reduce toxicities associated with conventional treatments, such as radiotherapy and chemotherapy. This approach has proved effectiv...

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Autores principales: Hawkins, Elizabeth R, D’Souza, Reena R, Klampatsa, Astero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053711/
https://www.ncbi.nlm.nih.gov/pubmed/33883875
http://dx.doi.org/10.2147/BTT.S291768
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author Hawkins, Elizabeth R
D’Souza, Reena R
Klampatsa, Astero
author_facet Hawkins, Elizabeth R
D’Souza, Reena R
Klampatsa, Astero
author_sort Hawkins, Elizabeth R
collection PubMed
description Chimeric antigen receptor (CAR) T-cell therapy engineers T-cells to express a synthetic receptor which redirects effector function to the tumor, to improve efficacy and reduce toxicities associated with conventional treatments, such as radiotherapy and chemotherapy. This approach has proved effective in treating hematological malignancies; however, the same effects have not been observed in solid tumors. The immunosuppressive tumor microenvironment (TME) creates a significant barrier to solid tumor efficacy and reduces the anti-cancer activity of endogenous tumor-resident immune cells, enabling cancer progression. In recent years, researchers have attempted to enhance CAR T-cell function in the TME by engineering the cells to express various proteins alongside the CAR. Examples of this engineering include inducing CAR T-cells to secrete cytokines or express cytokine receptors to modulate the cytokine milieu of the TME. Alternatively, the CAR T-cell may secrete antibody-like proteins to target a range of tumor antigens. Collectively, these methods are termed armored CAR T-cell therapy, and in this review, we will discuss the range of armored CAR T-cell approaches which have been investigated to date.
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spelling pubmed-80537112021-04-20 Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy Hawkins, Elizabeth R D’Souza, Reena R Klampatsa, Astero Biologics Review Chimeric antigen receptor (CAR) T-cell therapy engineers T-cells to express a synthetic receptor which redirects effector function to the tumor, to improve efficacy and reduce toxicities associated with conventional treatments, such as radiotherapy and chemotherapy. This approach has proved effective in treating hematological malignancies; however, the same effects have not been observed in solid tumors. The immunosuppressive tumor microenvironment (TME) creates a significant barrier to solid tumor efficacy and reduces the anti-cancer activity of endogenous tumor-resident immune cells, enabling cancer progression. In recent years, researchers have attempted to enhance CAR T-cell function in the TME by engineering the cells to express various proteins alongside the CAR. Examples of this engineering include inducing CAR T-cells to secrete cytokines or express cytokine receptors to modulate the cytokine milieu of the TME. Alternatively, the CAR T-cell may secrete antibody-like proteins to target a range of tumor antigens. Collectively, these methods are termed armored CAR T-cell therapy, and in this review, we will discuss the range of armored CAR T-cell approaches which have been investigated to date. Dove 2021-04-14 /pmc/articles/PMC8053711/ /pubmed/33883875 http://dx.doi.org/10.2147/BTT.S291768 Text en © 2021 Hawkins et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Review
Hawkins, Elizabeth R
D’Souza, Reena R
Klampatsa, Astero
Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy
title Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy
title_full Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy
title_fullStr Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy
title_full_unstemmed Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy
title_short Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy
title_sort armored car t-cells: the next chapter in t-cell cancer immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053711/
https://www.ncbi.nlm.nih.gov/pubmed/33883875
http://dx.doi.org/10.2147/BTT.S291768
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