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

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

Field of science

  • /medical and health sciences/health sciences/public and environmental health/epidemics prevention/immunisation
  • /medical and health sciences/clinical medicine/cancer
  • /medical and health sciences/medical biotechnology/cells technologies

Call for proposal

FP7-PEOPLE-2010-IOF
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Funding Scheme

MC-IOF - International Outgoing Fellowships (IOF)

Coordinator

INSTITUT CATALA D'ONCOLOGIA
Address
Av Gran Via De L'hospitalet 199-203
08908 L'hospitalet Del Llobregat
Spain
Activity type
Research Organisations
EU contribution
€ 223 669,60
Administrative Contact
Cris Rajo (Ms.)

Participants (1)

FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE

Participation ended

Spain
Address
Avenida Gran Via Hospitalet 199-203
08908 L'hospitalet De Llobregat
Activity type
Research Organisations
Administrative Contact
Victoria Cochrane (Ms.)