Final Report Summary - THERADPOX (Optimised and novel oncolytic adenoviruses and pox viruses in the treatment of cancer: Virotherapy combined with molecular chemotherapy) Cancer today is the second cause of disease-induced mortality worldwide. Among innovative treatments for cancer, virotherapy holds great promise. Virotherapy exploits an intrinsic feature of the lifecycle of oncolytic viruses (OVs): replication and spreading exclusively in tumour cells leading to their destruction, while not affecting normal cells. Clinical studies have demonstrated the safety and feasibility of this approach, but have shown only minimal therapeutic efficacy. Synergistic effects of combination treatments of OVs with chemo- and radiation therapy have been observed. Nevertheless, this approach still leaves patients subjected to the toxic adverse effects of chemotherapy and radiation. Thus, an unmet need exists for the improvement of current and the development of new treatment platforms leading to a significant increase in cure rates. Owing to their inherent strong oncolytic potency and safety record, pox-virus and adenovirus based vectors were chosen to pursue the goal of the THERADPOX project: to improve the safety and therapeutic efficacy of OVs in vivo. THERADPOX OVs were assessed for safety and non pathogenic effects in normal tissue and for efficacy in vitro on a panel of cancer cell lines (from the selected tumour models) and the selected tumour models in vivo in tumour bearing animals. In addition an original controlled delivery system was developed to increase the half-life of vectors in the circulation and to lower potential systemic toxicological side-effects. Moreover, a software application for fast, sharp, pertinent and standardised data analysis and interpretation was also developed within the consortium and distributed among partners. Various model oncolytic Pox and adenoviruses have been generated as proof of concept towards the development of oncolytic vectors with improved therapeutic efficacy. Through translational research, the project has generated an armamentarium of different oncolytic Pox and adenoviruses and different tools to enhance their tumour specificity. The translational research in this project has demonstrated proof of concept for oncolytic vectors with increased tumour selectivity of infection and viral spread through the tumour tissue. Documents connexes Final Report - THERADPOX (Optimised and novel oncolytic adenoviruses and pox viruses in the treatment of cancer: Virotherapy combined with molecular chemotherapy)
