Obiettivo 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. Campo scientifico medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicineradiologynuclear medicinemedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Programma(i) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Argomento(i) 5.4 - Somatic gene therapy Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore Rijksuniversiteit Leiden Contributo UE Nessun dato Indirizzo 151,Lange Kleiweg 2280 GG Leiden Paesi Bassi Mostra sulla mappa Costo totale Nessun dato Partecipanti (6) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto Academisch Ziekenhuis Rotterdam Paesi Bassi Contributo UE Nessun dato Indirizzo 301,Groene Hilledijk 3075 EA Rotterdam Mostra sulla mappa Costo totale Nessun dato Institut National de la Santé et de la Recherche Médicale Francia Contributo UE Nessun dato Indirizzo 8,Rue du Général Sarrail 94010 Créteil Mostra sulla mappa Costo totale Nessun dato KAROLINSKA INSTITUTE Svezia Contributo UE Nessun dato Indirizzo Haelsvaegen 7 141 57 Huddinge Mostra sulla mappa Costo totale Nessun dato University of Manchester Regno Unito Contributo UE Nessun dato Indirizzo Oxford Road M13 9PT Manchester Mostra sulla mappa Costo totale Nessun dato Université Libre de Bruxelles Belgio Contributo UE Nessun dato Indirizzo 808,Route de Lennik 1070 Bruxelles Mostra sulla mappa Costo totale Nessun dato Université Pierre et Marie Curie - Paris VI Francia Contributo UE Nessun dato Indirizzo 83,Boulevard de l'Hôpital 75651 Paris Mostra sulla mappa Costo totale Nessun dato