Objetivo Brain metastases occur in 20 to 35% of cancer patients and are associated with poor prognosis due to the lack of efficient treatments. Targeting of brain lesions poses several challenges including the poor penetration of drugs into the brain due to the tightness of the blood-brain barrier. Therefore improved approaches for the delivery of therapeutic agents to brain lesions are urgently required.The goal of this project is to develop a cell-based strategy to deliver therapeutic agents to brain metastases. This will be achieved by stable introduction of genes encoding secreted therapeutic molecules with anti-cancer properties into hematopoietic stem cells (HSCs). Upon transplantation, the progeny of HSCs will home to cancer lesions, thereby delivering the therapeutic agent of choice.We already demonstrated that the progeny of genetically engineered HSCs readily crosses the blood-brain barrier and homes to brain metastases in animal models where it efficiently expresses the delivered gene. Here we aim to further improve our approach in pre-clinical models to facilitate its clinical translation. To this end we aim to improve the efficiency of therapeutic delivery by increasing the infiltration of HSC progeny into the brain via whole brain radiation, a standard therapy for brain metastases. Secondly, we aim to improve the specificity of therapeutic delivery by identification of gene promoters that are active specifically within HSC progeny infiltrating the tumour. Expression of therapeutic agents by these promoters will restrict their delivery to tumour lesions. Thirdly, we aim to demonstrate a therapeutic efficacy of HSC-based drug delivery in combination with an enzyme / prodrug approach.Due to the advanced application of HSC transplantation and HSC-based cell therapies in the clinic, our approach has a strong potential for a successful clinical translation. Ámbito científico medical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinetransplantationnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Convocatoria de propuestas FP7-PEOPLE-2011-CIG Consulte otros proyectos de esta convocatoria Régimen de financiación MC-CIG - Support for training and career development of researcher (CIG) Coordinador UNIVERSITY OF LEEDS Aportación de la UE € 100 000,00 Dirección WOODHOUSE LANE LS2 9JT Leeds Reino Unido Ver en el mapa Región Yorkshire and the Humber West Yorkshire Leeds Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Martin Hamilton (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos