Objetivo The development of new viral vectors will focus on more efficient transduction and expression and on cell-type specific expression. Recombinant vectors containing mutant forms of herpes simplex thymidine kinase that are less toxic will be constructed and tested in vitro in combination with ganciclovir and novel antiherpetic nucleoside analogues. Vectors expressing the E. coli DeoD gene will be engineered and tested in combination with 6-methyl-purine-2'-deoxynucleoside. After studying the therapeutic index and bystander effect of these novel suicide gene/prodrug combinations in vitro, application in selected animal models will take place. Different routes of non-traumatic and more efficient viral vector delivery will be developed including systemic administration, convection enhanced intratumoral delivery and retrovirus producing cells embedded in biopolymers. These methods will be tested partly in vitro but mostly in a variety of animal models. In vivo imaging of the efficiency of suicide gene transfer is based on selective accumulation of some nucleoside analogues (including 5-iodo-2'-fluoro-2'-deoxy-arabinofuranosyluracil [FIAU]), after phosphorylation by herpes simplex thymidine kinase. Radiolabeled (14C, 125I, 18F) nucleoside analogues (FIAU) will first be tested in vitro using autoradiography and subsequently in vivo using autoradiography and SPECT/PET imaging. The bystander effect will be studied in vitro (above) and in vivo in brain tumour and multiple myeloma, Iymphoma and seminoma models. Modulation of the bystander effect will be attempted in vitro and in the multiple myeloma model by upregulation of connexins, molecules involved in gapjunction formation. The anti-tumor immune response elicited by suicide gene/prodrug treatment will be analyzed and modulated by cytokine (GM-CSF and IFNy) gene transfer. Ámbito científico medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicineradiologynuclear medicinemedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Programa(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Tema(s) 5.4 - Somatic gene therapy Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador Rijksuniversiteit Leiden Aportación de la UE Sin datos Dirección 151,Lange Kleiweg 2280 GG Leiden Países Bajos Ver en el mapa Coste total Sin datos Participantes (6) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Academisch Ziekenhuis Rotterdam Países Bajos Aportación de la UE Sin datos Dirección 301,Groene Hilledijk 3075 EA Rotterdam Ver en el mapa Coste total Sin datos Institut National de la Santé et de la Recherche Médicale Francia Aportación de la UE Sin datos Dirección 8,Rue du Général Sarrail 94010 Créteil Ver en el mapa Coste total Sin datos KAROLINSKA INSTITUTE Suecia Aportación de la UE Sin datos Dirección Haelsvaegen 7 141 57 Huddinge Ver en el mapa Coste total Sin datos University of Manchester Reino Unido Aportación de la UE Sin datos Dirección Oxford Road M13 9PT Manchester Ver en el mapa Coste total Sin datos Université Libre de Bruxelles Bélgica Aportación de la UE Sin datos Dirección 808,Route de Lennik 1070 Bruxelles Ver en el mapa Coste total Sin datos Université Pierre et Marie Curie - Paris VI Francia Aportación de la UE Sin datos Dirección 83,Boulevard de l'Hôpital 75651 Paris Ver en el mapa Coste total Sin datos