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| Status |
Public on Apr 04, 2024 |
| Title |
A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The majority of common chronic human diseases remain incurable, impacting a significant portion of the population and necessitating lifelong treatments that impose a substantial burden on health, the economy, and society. Asthma, the most prevalent respiratory disease, exemplifies this challenge, affecting over 300 million people and causing more than 250,000 deaths annually. Here, we demonstrate the achievement of long-term remission of type 2-high asthma through a single infusion of engineered CAR T cells. By utilizing IL-5 as the targeting domain and depleting BCOR and ZC3H12A, we engineer long-lived CAR T cells designed to eradicate IL-5R+ eosinophils, termed Immortal-like and Functional IL-5 CAR T (5TIF) cells. Furthermore, we enhance 5TIF cells by engineering them to secrete an IL-4 mutein that blocks the signaling of both IL-4 and IL-13, two inflammatory cytokines driving asthma pathology, resulting in the creation of 5TIF4 cells. In multiple asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, leads to long-term depletion of pathological eosinophils and blockade of IL-4/IL-13 actions. This results in sustained repression of type 2 inflammation and alleviation of asthmatic symptoms. Additionally, 5TIF4 cells can be induced in human T cells in NSG mice. These findings demonstrate that asthma, a prevalent and incurable disease, can undergo durable remission through a single infusion of engineered CAR T cells. This breakthrough paves the way for the potential functional cure of chronic noncancerous diseases using long-lived CAR T cells.
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| Overall design |
In order to study the molecular mechanisms of unconstained expasion and long-term persistence of 5TIF in mice and IL-4 mutein's influence on 5TIF cell phenotypes, we performed bulk-RNA seq assay for Endogenous CD8 T cell from PBS group, 5TIF cells and 5TIF4 cells.
One month after cell transfer, CD8+ Thy1.1+ 5TIF, 5TIF4 cells or endogenous CD8+ T cells were sorted by flow cytometry with purity > 95% from spleen of recipient mice. RNA samples were isolated and purified using TIANGEN RNAprep Pure Cell/Bacteria Kit, then shipped to BGI for library preparation and RNA sequencing on a DNBseq™.
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| Contributor(s) |
Jin G, Peng M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Mar 25, 2024 |
| Last update date |
Apr 04, 2024 |
| Contact name |
Gang Jin |
| E-mail(s) |
kim_gang@yeah.net
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| Organization name |
Tsinghua University
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| Department |
Institute for Immunology
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| Lab |
Lab of Min Peng
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| Street address |
Zhongguancun North street
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| City |
Beijing |
| ZIP/Postal code |
100084 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1091579 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE262359_Gene_read_counts_matrix.txt.gz |
291.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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