Objective
New treatment modalities are needed to augment present therapies for metastasising colorectal cancer. The TNF-related-apoptosis-inducing ligand (TRAIL; ApoL2) has been shown to specifically induce cell death in tumour cells, including colorectal cancer cel ls, leaving normal healthy tissue unaffected. Gene therapy approaches using TRAIL have the advantage over bolus injections of recombinant protein, that the cytokine can continuously exert its anti-tumour effect. However, clinical gene therapy applications have been hampered by a combination of side effects and poor delivery. One way to overcome this hurdle is to utilise the functions of stem cells drawn upon by the growing tumour, i.e. tumours require formation of supportive mesenchymal stroma and exogenously delivered mesenchymal stem cells (MSC) preferentially engraft at the tumour sites and contribute to the population of stromal fibroblasts.
Our goal is to transduce MSCs with an expression construct carrying an engineered, secreted version of TRAIL. The MSCs will be transduced ex vivo with Adeno-associated viral (AAV) vectors that are known to facilitate long-term gene expression and trigger no substantial immune responses. The AAV vectors will be optimised for the transduction of MSC by the use of bi-specific antibodies and a bio-selection procedure.
This procedure aims to isolate mutants that show improved transduction of MSC. Finally the TRAIL-loaded MSC will be tested in various colon cancer models for efficacy and safety. In summary we will engineer a combined cell-gene therapy system combining the safety features of AAV and TRAIL and the tumour-delivery potential of MSCs, which we will further enhance by chemokine-guided recruitment to the tumour. In order to reach our goal of combating colon cancer u sing adult stem cells and modern vector technology, I wish to build an international research team at the National University of Ireland, Galway.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences clinical medicine oncology lung cancer
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology colorectal cancer
- medical and health sciences clinical medicine oncology pancreatic cancer
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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.
FP6-2005-MOBILITY-8
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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
GALWAY
Ireland
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.