ANTITUMOR IMMUNITY

An in-vivo RNAi approach to identify and evaluate suppressors of anti-tumor T cell immunity

Coordinatore	FORSCHUNGSINSTITUT FUER MOLEKULARE PATHOLOGIE Ges.m.b.H    more  Organization address address: Dr. Bohr-Gasse 7 city: VIENNA postcode: 1030 contact info Titolo: Mrs. Nome: Tanja Cognome: Winkler Email: send email Telefono: +43 1 79044 4410 Fax: +43 1 79871 56
Nazionalità Coordinatore	Austria [AT]
Totale costo	186˙783 €
EC contributo	186˙783 €
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-IEF
Funding Scheme	MC-IEF
Anno di inizio	2015
Periodo (anno-mese-giorno)	2015-02-15   -   2017-02-14

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FORSCHUNGSINSTITUT FUER MOLEKULARE PATHOLOGIE Ges.m.b.H  Organization address address: Dr. Bohr-Gasse 7 city: VIENNA postcode: 1030 contact info Titolo: Mrs. Nome: Tanja Cognome: Winkler Email: send email Telefono: +43 1 79044 4410 Fax: +43 1 79871 56	AT (VIENNA)	coordinator	186˙783.60

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 Obiettivo del progetto (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.'