Cel 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 Dziedzina nauki medical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesmedical biotechnologycells technologies Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2010-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development" Zaproszenie do składania wniosków FP7-PEOPLE-2010-IOF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IOF - International Outgoing Fellowships (IOF) Koordynator INSTITUT CATALA D'ONCOLOGIA Wkład UE € 223 669,60 Adres AV GRAN VIA DE L'HOSPITALET 199-203 08908 L'HOSPITALET DEL LLOBREGAT Hiszpania Zobacz na mapie Region Este Cataluña Barcelona Rodzaj działalności Research Organisations Kontakt administracyjny Cris Rajo (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE Zakończenie uczestnictwa Hiszpania Wkład UE Brak danych Adres AVENIDA GRAN VIA HOSPITALET 199-203 08908 L'Hospitalet De Llobregat Zobacz na mapie Region Este Cataluña Barcelona Rodzaj działalności Research Organisations Kontakt administracyjny Victoria Cochrane (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych