Objectif 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 Champ scientifique medical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesmedical biotechnologycells technologies 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) Thème(s) FP7-PEOPLE-2010-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Appel à propositions FP7-PEOPLE-2010-IOF Voir d’autres projets de cet appel Régime de financement MC-IOF - International Outgoing Fellowships (IOF) Coordinateur INSTITUT CATALA D'ONCOLOGIA Contribution de l’UE € 223 669,60 Adresse AV GRAN VIA DE L'HOSPITALET 199-203 08908 L'HOSPITALET DEL LLOBREGAT Espagne Voir sur la carte Région Este Cataluña Barcelona Type d’activité Research Organisations Contact administratif Cris Rajo (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE Participation terminée Espagne Contribution de l’UE Aucune donnée Adresse AVENIDA GRAN VIA HOSPITALET 199-203 08908 L'Hospitalet De Llobregat Voir sur la carte Région Este Cataluña Barcelona Type d’activité Research Organisations Contact administratif Victoria Cochrane (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée