Journal
CELL DISCOVERY
Volume 8, Issue 1, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41421-022-00433-y
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Funding
- National Key R&D Program of China [2021YFC2700604, 2021YFA1102000]
- National Natural Science Foundation of China [81920108001, 81870007]
- Zhejiang Provincial Natural Science Foundation [LD19H160001]
- Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [WKJ-ZJ-2213]
- Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents [2016-63]
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This study presents a cell-based treatment strategy for severe eosinophilic asthma by engineering a cytokine-anchored chimeric antigen receptor T cell system. The treatment showed long-lasting protection against asthma-related conditions and has the potential to be used in precision therapies for other intractable allergic diseases.
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-CD3 zeta 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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