Objective
Killing of cancer cells with an oncolytic adenovirus is an immunogenic phenomenon and can therefore be utilized for breaking the immunological tolerance of a tumor.
Two complementary strategies can be used to enhance the T cell response towards the tumor: A) recruiting Dendritic Cells (DCs) to the tumor site to augment peptide loading onto MHC I; B) specific activation of DCs at the tumor site to increase their expression of co-stimulatory molecules for enhancement of cross-priming and T cell activation rather than cross-tolerance.
As our first aim, we propose to generate three different capsid-modified oncolytic vectors expressing granulocyte-macrophage colony-stimulating factor (GM-CSF). The transgene will be driven by a replication-coupled adenoviral promoter to ensure GM-CSF production exclusively in tumor cells (an oncolytic virus replicates only in tumor cells). GM-CSF is a potent cytokine that enhances the function of antigen presenting cells (APCs) by the maturation, activation, and recruitment of DCs, macrophages and monocytes.
All biologic responses crucial for DC functioning are influenced by signaling through the Toll-like receptors (TLRs), and TLR9 in particular is a key bridge between the innate and adaptive response. We propose, as our second aim, to generate an oncolytic vector containing CpG-stimulating sequences in its genome to combine oncolytic cell killing with effective delivery of CpG DNA to the endosome, where TLR9 is located.
Finally, we will combine the two strategies described in aims 1 and 2, generating oncolytic vectors that are able to secrete GM-CSF for recruiting APCs to the tumor and at the same time to stimulate TLR9 in these cells. Overall we propose to capitalize on the entry biology of adenovirus for stimulation of TLR9 coupled with tumor specific secretion of immunomodulatory molecules to orchestrate immune rejection of the tumor.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-IRG-2008
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
00014 HELSINGIN YLIOPISTO
Finland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.