Objective The immune system plays a major role in safeguarding us from cancer. Tumor progression is closely linked to functional suppression of T cell responses, and strategies to reactivate tumor-specific CD8+ T cells hold great promise for cancer therapy, as evidenced by recent clinical breakthroughs. However, the further exploration of such therapies is hampered by our incomplete understanding of key genes and pathways involved in suppression of anti-tumor T cell immunity. Here, we propose an innovative approach combining three well-established experimental systems - genetically engineered mouse models of human cancer, T cell receptor/cognate antigen transgenic mice, and advanced in-vivo RNAi screening technologies - to systematically identify and functionally evaluate genes involved in this process. Specifically, we will establish an experimentally scalable in-vivo RNAi system to investigate genes modulating interactions between OT-I transgenic T cells and cOVA expressing cancer models, and use it in a multiplex in-vivo RNAi screen to survey a focused shRNA library targeting ~400 candidate T cell suppressor genes. Using this innovative screening approach and a sequential functional validation strategy, we seek to identify and functionally study new factors involved in the suppression of anti-tumor T cell immunity, ultimately to guide the development of more effective targeted cancer therapies. Fields of science medical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineoncology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2013-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH EU contribution € 186 783,60 Address CAMPUS-VIENNA-BIOCENTER 1 1030 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Tanja Winkler (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
