Obiettivo 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. Campo scientifico medical and health sciencesclinical medicineoncologylung cancernatural scienceschemical sciencesinorganic chemistrypost-transition metalsmedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicineimmunologyimmunotherapy Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Invito a presentare proposte ERC-2013-StG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante KING'S COLLEGE LONDON Contributo UE € 1 499 994,00 Indirizzo STRAND WC2R 2LS London Regno Unito Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Paul Labbett (Mr.) Ricercatore principale James Noble Arnold (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto KING'S COLLEGE LONDON Regno Unito Contributo UE € 1 499 994,00 Indirizzo STRAND WC2R 2LS London Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Paul Labbett (Mr.) Ricercatore principale James Noble Arnold (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
