CANCER THERAPIES

Use of adoptive T cell transfer in combination with oncolytic adenoviruses for cancer treatment

Coordinatore	INSTITUT CATALA D'ONCOLOGIA    more  Organization address address: "AVDA. Gran Via KM 2,7 S/N" city: "HOSPITALET DEL LLOBREGAT, BARCELONA" postcode: 8907 contact info Titolo: Ms. Nome: Cris Cognome: Rajo Email: send email Telefono: 34932607812 Fax: 34932607787
Nazionalità Coordinatore	Spain [ES]
Totale costo	223˙669 €
EC contributo	223˙669 €
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-2010-IOF
Funding Scheme	MC-IOF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-05-01   -   2015-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT CATALA D'ONCOLOGIA  Organization address address: "AVDA. Gran Via KM 2,7 S/N" city: "HOSPITALET DEL LLOBREGAT, BARCELONA" postcode: 8907 contact info Titolo: Ms. Nome: Cris Cognome: Rajo Email: send email Telefono: 34932607812 Fax: 34932607787	ES ("HOSPITALET DEL LLOBREGAT, BARCELONA")	coordinator	223˙669.60
2	FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE  Organization address address: AVENIDA GRAN VIA HOSPITALET 199-203 city: L'HOSPITALET DE LLOBREGAT postcode: 8908 contact info Titolo: Ms. Nome: Victoria Cognome: Cochrane Email: send email Telefono: 34932607226	ES (L'HOSPITALET DE LLOBREGAT)	participant	0.00

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 Obiettivo del progetto (Objective)

'Metastatic cancer remains an incurable disease in the majority of cases and thus development of novel treatment strategies is required. Adoptive T cell therapy is a promising therapy for patients with a wide range of cancers. This therapy involves ex vivo activation and expansion of T cells followed by infusion into patients. Peripheral blood CD4 and CD8 T cells can be redirected against tumor-associated antigens (TAA) by genetically modifying them with chimeric antigen receptors (CARs). Commonly, CARs consist of an antibody-based external receptor structure coupled to an intracellular signaling domain. Recent clinical studies using CAR-modified cells have established the feasibility and safety of this strategy in human patients. However, several hurdles have still to be overcome for a successful tumor treatment with this therapy. First, infused CAR-modified cells have short persistence in the host, limiting antitumor responses. And second, tumor creates a strong immunosuppressive environment that can impair the efficacy of infused T cells. Our hypothesis in the proposed program is that persistence and efficacy of genetically modified T cells in cancer patients can be increased by: (1) choosing the “right” T cell subset candidate (2) improving the signaling endodomain of CARs, (3) breaking tumor immunotolerance. In this regard, we propose that oncolytic adenoviruses, whose replication has been restricted to malignant cells, can be used to enhance tumor immunotherapy as they offer (a) tumor debulking and (b) danger signals that elicit strong immune responses. In order to test these hypothesis, the proposed program aims to (1) evaluate the contribution of different costimulatory signalling domains to CAR T cell function, (2) compare the in vivo engraftment, trafficking, persistence and efficacy of different subsets of engineered CD4 and CD8 T cells, including Th1, Th2, Th17 and Tc17 cells in tumor bearing mice, (3) Evaluate the ability of oncolytic adenoviruses e'