Objective
The therapeutic vaccination against breast cancer, and more widely all solid tumours, has largely been ineffective in clinical trials. This failure has been attributed to ‘immune editing’ of the cancerous cells, or to suppression of T cell functions within the tumour. In relation to the later, we have identified a novel population of tumoural macrophages, marked by the expression of fibroblast activation protein-alpha (FAP) which can mediate tumoural immune suppression through the enzyme heme oxygenase-1 (HO-1). Selective inhibition of HO-1 with tin mesoporphyrin (SnMP), a drug which has already been administered to infants for the treatment of neonatal jaundice, permits immunological control of tumour growth in transplantable Lewis lung carcinoma tumours. This proposal seeks to evaluate SnMP as a novel cancer immunotherapy for the treatment of breast cancer. We have demonstrated that HO-1+ cells are recruited into mammary tumours of a relevant spontaneous murine model of breast cancer. A vaccine strategy will be developed targeting telomerase, a vaccine target already in clinical trial for human breast cancer. The effect on mammary tumour growth of a vaccine induced anti-tumour immune response, alongside HO-1 inhibition to alleviate immune suppression, will be assessed. Lung metastases in these mice, and their response to treatment, will also be studied. The HO-1 expressing cells in human breast cancer will be quantitated and characterised at both the protein and transcriptome levels to validate the approach. Novel immuno-therapies directed at modulating HO-1 expression will also be investigated, facilitated by the development of a transgenic HO-1 reporter mouse which will co-express green fluorescent protein and luciferase driven by the promoter and response elements of the HO-1 gene. As cancer vaccines have already been developed, and as we have identified a drug, SnMP, which may circumvent tumoural immune suppression, this proposal is clinically relevant.
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 clinical medicine oncology lung cancer
- natural sciences chemical sciences inorganic chemistry post-transition metals
- medical and health sciences clinical medicine oncology breast cancer
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine immunology immunotherapy
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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.
ERC-2013-StG
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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.
Host institution
WC2R 2LS London
United Kingdom
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.