EGF-R for immunity · Use of EGF-R antagonists for the treatment of chronic infections and tumor growth
FP7 — People (Marie Curie Actions)
- Duration
- 2014-03-01 → 2018-02-28
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
Use of EGF-R antagonists for the treatment of chronic infections and tumor growth
Key aspect with regard to the aim of the CIG funding scheme has been to integrate a researcher from one European country into the scientific community of another European country. The CIG “EGF-R for Immunity” clearly achieved this aim. The grantee moved in Autumn 2013 to the UK to fill a faculty position at the University of Edinburgh. He established a very productive Lab of about seven people, became tenured and promoted to the position of a Reader (Associated Professor) in Immunology. Within the funding period of the CIG grant he attracted 8 additional research grants and published 11 peer-reviewed publications in such high-profile journals as Immunity (Zaiss et al. 2015 or Minutti et al. 2017), Science (Minutti et al. 2017), PNAS (Monticelli et al. 2015) or the Journal of Clinical Investigation (Bruce 2017). In the period of the grant funding the grantee supervised 3 PhD students, 3 Master by Research students and 8 undergraduate research project students. These different researchers have worked either directly on those research Aims as they have been described in the CIG proposal or work on topics, which are closely related to this project and address the function of the EGF-R in the immune system (as it is suggested by the CIG acronym “EGF-R for Immunity”). In line with these scientific progress the grantee has been invited to give presentations at 13 different Universities and Research Centers nationally (within the UK), within Europe and worldwide. Furthermore, he gave twice oral presentations at the annual conference of the national/British society of Immunologists and presented his work on the local radio and evening news (BBC Scotland) and twice to a selection of Scottish members of Parliament. Furthermore, the grantee organized a European-wide ITN grant proposal, which was then finally funded in 2017, established a consortium to develop inhibitors against the EGF-like growth factor Amphiregulin and to test these in a preclinical setting. To develop these inhibitors further the grantee got in contact with different European pharmaceutical companies, such as Boehringer Ingelheim.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- THE UNIVERSITY OF EDINBURGH · EdinburghCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union