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Contenido archivado el 2024-06-18

Use of EGF-R antagonists for the treatment of chronic infections and tumor growth

Objetivo

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.

Ámbito científico (EuroSciVoc)

Programa(s)

Tema(s)

Convocatoria de propuestas

FP7-PEOPLE-2013-CIG
Consulte otros proyectos de esta convocatoria

Régimen de financiación

MC-CIG - Support for training and career development of researcher (CIG)

Coordinador

THE UNIVERSITY OF EDINBURGH
Aportación de la UE
€ 100 000,00
Dirección
OLD COLLEGE, SOUTH BRIDGE
EH8 9YL Edinburgh
Reino Unido
Región
Scotland Eastern Scotland Edinburgh
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos