Journal article
A Granzyme B-Cleavable T Cell-Targeted Bispecific Cell Vesicle Connector for Reversing New-Onset Type 1 Diabetes
Journal of the American Chemical Society, v 147(5), pp 4167-4179
27 Jan 2025
PMID: 39869523
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Type 1 diabetes (T1D) is an autoimmune disorder in which pancreatic β-cells are destroyed by CD8
T cells. Anti-CD3 antibody effectively treats early-stage T1D when β-cell autoantibodies are detected but before symptoms appear. However, it impairs the immune system temporarily, exposing individuals to infection. A therapeutic that can reverse new-onset T1D without harming the immune system remains urgently needed. Herein, we have constructed cellular vesicles presenting granzyme B-responsive fusion proteins (designated aCD8-GrzBcs-IL2) composed of a single-chain variable fragment of anti-CD8 antibodies and a mutein interleukin-2 (IL2). aCD8-GrzBcs-IL2 is designed to simultaneously inhibit CD8
T cells and promote Treg cells, especially when CD8
T cells are attacking β-cells.
, these cellular vesicles can inhibit the cell-killing effect of CD8
T cells and enhance the expansion of Treg cells. Notably, intravenous administration of aCD8-GrzBcs-IL2-expressed cellular vesicles reversed newly onset diabetes in 77.8% of nonobese diabetic (NOD) mice without reducing blood CD3
T cells and CD8
T cells, indicating a favorable safety profile.
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Details
- Title
- A Granzyme B-Cleavable T Cell-Targeted Bispecific Cell Vesicle Connector for Reversing New-Onset Type 1 Diabetes
- Creators
- Yanfang Wang - Zhejiang UniversityYanping Sun - Zhejiang UniversityXiuwen Zhang - Zhejiang UniversityShenqiang Wang - Zhejiang UniversityXuehui Huang - Zhejiang UniversityKairui Xu - Zhejiang UniversityYun Liu - Zhejiang UniversityYingqi Huang - Zhejiang UniversityJianchang Xu - Zhejiang UniversityXinwei Wei - Zhejiang UniversityHao Cheng - Drexel UniversityLiqiang Pan - Zhejiang UniversityJinqiang Wang - Zhejiang UniversityZhen Gu - Zhejiang University
- Publication Details
- Journal of the American Chemical Society, v 147(5), pp 4167-4179
- Publisher
- AMER CHEMICAL SOC
- Number of pages
- 13
- Grant note
- JDRF: 2021YFA0909900 National Key R&D Program of China: 2023YFC3403900 National Key R&D Program of China: 82073750, 82473824, 52233013 National Natural Science Foundation of China: zz202303 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases: SN-ZJU-SIAS-009 Shanghai Institute for Advanced Study of Zhejiang University: 2024C03083, 2024C03085, 2024C03168 Key Project of the Science and Technology Commission of Zhejiang Province
This work was supported by grants from the National Key R&D Program of China (2021YFA0909900), National Key R&D Program of China (2023YFC3403900), National Natural Science Foundation of China (82073750, 82473824, and 52233013), State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (zz202303), the Starry Night Science Fund at the Shanghai Institute for Advanced Study of Zhejiang University (SN-ZJU-SIAS-009), and the Key Project of the Science and Technology Commission of Zhejiang Province (2024C03083, 2024C03085, and 2024C03168).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:001406980700001
- Scopus ID
- 2-s2.0-85216487582
- Other Identifier
- 991022024311004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary