THOVLEN - Targeted Herpesvirus-derived Oncolytic Vectors for Liver cancer European Network (FP6-LIFESCIHEALTH) (2006-01-01 - 2008-12-31) (»add to infobox)

Alberto EPSTEIN, Roberto MANSERVIGI, Andres CRESPO, Ruben HERNANDEZ-ALCOCEBA, Thomas BROCKER, Penelope MAVROMARA, Jean-Jacques DIAZ

UNIVERSITE CLAUDE BERNARD LYON 1 (FR716 - Rhône) (France), UNIVERSITA DEGLI STUDI DI FERRARA (ITD56 - Ferrara) (Italy), GENOPOIETIC SAS (FR711 - Ain) (France), FUNDACION PARA LA INVESTIGACION MED ICA APLICADA FIMA (ES220 - Navarra) (Spain), LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN (DE212 - München, Kreisfreie Stadt) (Germany), HELLENIC PASTEUR INSTITUTE (GR300 - Attiki) (Greece), NUCLEALP (FR718 - Haute-Savoie) (France)

The overall objective of THOVLEN is to develop safe and efficient herpes simplex virus type 1 (HSV-1)-derived oncolytic vectors, designed to strictly target and eradicate human hepatocellular carcinomas (HCC), the most common liver cancer of adults. HSV-1 is certainly one of the most promising viral platforms for the development of improved oncolytic vectors, as anticipated by the unique biological properties of this virus and confirmed by the encouraging results coming from clinical trials in gliomas. However, the first generations of oncolytic HSV-1 vectors have also shown limitations regarding efficacy and safety. New generations of innovative HSV-1 vectors with improved potency and safety are required before the oncolytic strategy using HSV-1 becomes a standard therapeutic reality against cancer, and this is the goal of THOVLEN. One of the most important innovative contributions of our project concerns the overall approach towards the improvement of HSV-1-based oncolytic viruses. Instead of focusing on the development of vectors carrying deletions in particular virus genes, we will engineer competent, but replication-restricted, HSV-1 vectors, strictly targeted to HCC. These vectors will combine multiple HCC-targeting approaches, both at the level of entry and at the level of gene expression and replication, and will be able to multiply and spread only in HCC, while displaying no virulence in normal healthy tissues. Additionally, an important innovation is related to the ability of the HSV-1 vectors to permit a sophisticated and flexible combined approach against HCC. That is, in addition to optimizing the oncolytic properties of HSV-1 vectors, THOVLEN will exploit the very large transgenic capability of HSV-1 to generate vectors that will simultaneously display multiple and multimodal anti-tumour activities acting either locally or systemically, including combined expression of anti-angiogenic, immune-modulatory, and oncolytic pr

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