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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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Detalles Bibliográficos
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
Descripción
Sumario: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.