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Journal article
Superior Treg-Expanding Properties of a Novel Dual-Acting Cytokine Fusion Protein
Frontiers in pharmacology, v 10, pp 1490-1490
18 Dec 2019
PMID: 31920671
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Autoimmune diseases are caused by uncontrolled endogenous immune responses against healthy cells. They may develop due to an impaired function of regulatory T cells (Tregs), which normally suppress self-specific effector immune cells. Interleukin 2 (IL-2) and tumor necrosis factor (TNF) have been identified as key players that promote expansion, function, and stability of Tregs.
In vivo
, both low-dose IL-2 therapy and TNF receptor 2 (TNFR2) agonism were shown to expand Tregs and alleviate autoimmunity. We here designed a novel dimeric dual-acting fusion cytokine, where mouse IL-2 is genetically linked to a TNFR2-selective single-chain TNF mutein (IL2-EHD2-sc-mTNF
R2
). IL2-EHD2-sc-mTNF
R2
showed high affinity to TNFR2 and efficiently activated IL-2 and TNFR2-selective signaling pathways. Further, IL2-EHD2-sc-mTNF
R2
promoted superior Treg expansion, with both the IL-2 and the TNFR2 agonist (sc-mTNF
R2
) component necessary for this biological response. Ultimately, we propose that IL2-EHD2-sc-mTNF
R2
is a dual-acting cytokine that efficiently promotes Treg expansion and might have a superior therapeutic window than conventional IL-2-based drugs.
Metrics
Details
- Title
- Superior Treg-Expanding Properties of a Novel Dual-Acting Cytokine Fusion Protein
- Creators
- Tanja Padutsch - University of StuttgartMaksim Sendetski - University of StuttgartCarina Huber - University of StuttgartNathalie Peters - University of StuttgartKlaus Pfizenmaier - University of StuttgartJohn R. Bethea - Drexel UniversityRoland E. Kontermann - University of StuttgartRoman Fischer - Drexel University
- Publication Details
- Frontiers in pharmacology, v 10, pp 1490-1490
- Publisher
- Frontiers Media S.A
- Grant note
- Carl-Zeiss-Stiftung Deutsche Forschungsgemeinschaft
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000504979900001
- Scopus ID
- 2-s2.0-85077383840
- Other Identifier
- 991019168698904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy