EGF-R FOR IMMUNITY
Use of EGF-R antagonists for the treatment of chronic infections and tumor growth
| Coordinatore | THE UNIVERSITY OF EDINBURGH
Organization address
address: OLD COLLEGE, SOUTH BRIDGE contact info |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2013-CIG |
| Funding Scheme | MC-CIG |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-03-01 - 2018-02-28 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE UNIVERSITY OF EDINBURGH
Organization address
address: OLD COLLEGE, SOUTH BRIDGE contact info |
UK (EDINBURGH) | coordinator | 100˙000.00 |
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Obiettivo del progetto (Objective)
'FoxP3 expressing regulatory T-cells play an important role in the induction of peripheral tolerance and the prevention of auto-immune responses. How the functionality of regulatory T-cells is regulated at the site of inflammation remains poorly understood. We just recently discovered that the functionality of regulatory T-cells is regulated via the EGF-R that is expressed by activated regulatory T-cells. In in vitro suppression assays the presence of the EGF-like growth factor Amphiregulin significantly enhanced the suppressive capacity of regulatory T-cells and, in vivo, Amphiregulin-induced signals enabled regulatory T-cells to induce tolerance against innocuous antigens. This effect was blocked upon application of EGF-R antagonists (Zaiss et al. 2013). Based on these findings, the objectives of this proposal are: 1.a) To determine the role of regulatory T-cells during tumor therapy; in specific during induced lymphopenia in the context of adoptive cell transfer (ACT) based tumor therapy. 1.b) To determine whether EGF-R inhibitors can suppress regulatory T-cell function such that they enhance the efficacy of ACT based tumor therapy? 2) To determine whether smallpox viruses use their virus-encoded EGF-like growth factors to enhance regulatory T-cell function, and thus as an immune escape mechanism? This will answer the question whether interference with regulatory T-cell function explains for the immune-stimulatory effect of EGF-R inhibitor treatment, during vaccinia virus infections. 3) To determine whether we can develop an EGF-R inhibitor that selectively targets regulatory T-cells, and thus keeps all other functions of the EGF-R, for example in tissue homeostasis, intact?
Taken together, this proposed project tests a novel therapeutic approach by which we expect to have hit a so far unrecognized, therapeutic “Achilles’ heel” of Tregs, i.e. via the regulation of Treg functionality by EGF-R ligands.'