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Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells

Severe eosinophilic asthma (SEA) is a therapy-resistant respiratory condition with poor clinical control. Treatment efficacy and patient compliance of current therapies remain unsatisfactory. Here, inspired by the remarkable success of chimeric antigen receptor-based cellular adoptive immunotherapie...

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Autores principales: Chen, Sisi, Chen, Gaoying, Xu, Fang, Sun, Beibei, Chen, Xinyi, Hu, Wei, Li, Fei, Syeda, Madiha Zahra, Chen, Haixia, Wu, Youqian, Wu, Peng, Jing, Ruirui, Geng, Xinwei, Zhang, Lingling, Tang, Longguang, Li, Wen, Chen, Zhihua, Zhang, Chao, Sun, Jie, Chen, Wei, Shen, Huahao, Ying, Songmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381771/
https://www.ncbi.nlm.nih.gov/pubmed/35973984
http://dx.doi.org/10.1038/s41421-022-00433-y
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author Chen, Sisi
Chen, Gaoying
Xu, Fang
Sun, Beibei
Chen, Xinyi
Hu, Wei
Li, Fei
Syeda, Madiha Zahra
Chen, Haixia
Wu, Youqian
Wu, Peng
Jing, Ruirui
Geng, Xinwei
Zhang, Lingling
Tang, Longguang
Li, Wen
Chen, Zhihua
Zhang, Chao
Sun, Jie
Chen, Wei
Shen, Huahao
Ying, Songmin
author_facet Chen, Sisi
Chen, Gaoying
Xu, Fang
Sun, Beibei
Chen, Xinyi
Hu, Wei
Li, Fei
Syeda, Madiha Zahra
Chen, Haixia
Wu, Youqian
Wu, Peng
Jing, Ruirui
Geng, Xinwei
Zhang, Lingling
Tang, Longguang
Li, Wen
Chen, Zhihua
Zhang, Chao
Sun, Jie
Chen, Wei
Shen, Huahao
Ying, Songmin
author_sort Chen, Sisi
collection PubMed
description Severe eosinophilic asthma (SEA) is a therapy-resistant respiratory condition with poor clinical control. Treatment efficacy and patient compliance of current therapies remain unsatisfactory. Here, inspired by the remarkable success of chimeric antigen receptor-based cellular adoptive immunotherapies demonstrated for the treatment of a variety of malignant tumors, we engineered a cytokine-anchored chimeric antigen receptor T (CCAR-T) cell system using a chimeric IL-5-CD28-CD3ζ receptor to trigger T-cell-mediated killing of eosinophils that are elevated during severe asthma attacks. IL-5-anchored CCAR-T cells exhibited selective and effective killing capacity in vitro and restricted eosinophil differentiation with apparent protection against allergic airway inflammation in two mouse models of asthma. Notably, a single dose of IL-5-anchored CCAR-T cells resulted in persistent protection against asthma-related conditions over three months, significantly exceeding the typical therapeutic window of current mAb-based treatments in the clinics. This study presents a cell-based treatment strategy for SEA and could set the stage for a new era of precision therapies against a variety of intractable allergic diseases in the future.
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spelling pubmed-93817712022-08-18 Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells Chen, Sisi Chen, Gaoying Xu, Fang Sun, Beibei Chen, Xinyi Hu, Wei Li, Fei Syeda, Madiha Zahra Chen, Haixia Wu, Youqian Wu, Peng Jing, Ruirui Geng, Xinwei Zhang, Lingling Tang, Longguang Li, Wen Chen, Zhihua Zhang, Chao Sun, Jie Chen, Wei Shen, Huahao Ying, Songmin Cell Discov Article Severe eosinophilic asthma (SEA) is a therapy-resistant respiratory condition with poor clinical control. Treatment efficacy and patient compliance of current therapies remain unsatisfactory. Here, inspired by the remarkable success of chimeric antigen receptor-based cellular adoptive immunotherapies demonstrated for the treatment of a variety of malignant tumors, we engineered a cytokine-anchored chimeric antigen receptor T (CCAR-T) cell system using a chimeric IL-5-CD28-CD3ζ receptor to trigger T-cell-mediated killing of eosinophils that are elevated during severe asthma attacks. IL-5-anchored CCAR-T cells exhibited selective and effective killing capacity in vitro and restricted eosinophil differentiation with apparent protection against allergic airway inflammation in two mouse models of asthma. Notably, a single dose of IL-5-anchored CCAR-T cells resulted in persistent protection against asthma-related conditions over three months, significantly exceeding the typical therapeutic window of current mAb-based treatments in the clinics. This study presents a cell-based treatment strategy for SEA and could set the stage for a new era of precision therapies against a variety of intractable allergic diseases in the future. Springer Nature Singapore 2022-08-16 /pmc/articles/PMC9381771/ /pubmed/35973984 http://dx.doi.org/10.1038/s41421-022-00433-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Sisi
Chen, Gaoying
Xu, Fang
Sun, Beibei
Chen, Xinyi
Hu, Wei
Li, Fei
Syeda, Madiha Zahra
Chen, Haixia
Wu, Youqian
Wu, Peng
Jing, Ruirui
Geng, Xinwei
Zhang, Lingling
Tang, Longguang
Li, Wen
Chen, Zhihua
Zhang, Chao
Sun, Jie
Chen, Wei
Shen, Huahao
Ying, Songmin
Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
title Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
title_full Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
title_fullStr Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
title_full_unstemmed Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
title_short Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
title_sort treatment of allergic eosinophilic asthma through engineered il-5-anchored chimeric antigen receptor t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381771/
https://www.ncbi.nlm.nih.gov/pubmed/35973984
http://dx.doi.org/10.1038/s41421-022-00433-y
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