TG6002: A novel oncolytic and vectorized gene pro-drug therapy approach to treat glioblastoma.

e13510Background: Glioblastoma (GBM) is an incurable disease challenging innovations for significant therapeutic progress. TG6002 is a vaccinia virus that replicates mainly in tumor cells after deletion of genes coding for thymidine kinase and ribonucleotide reductase. TG6002 alsoexpresses the yeast-originated gene FCU1 encoding cytosine deaminase and uracilphosphoribosyltransferase that transforms the pro-drug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluoro-uridilyl monophosphate (5-FUMP), respectively. The proof of this ‘suicide gene’ concept has been demonstrated in man, using a non-replicative vaccinia virus hosting the FCU1gene (Husseini F et al, ASCO 2012). TG6002 mechanism of action then associates oncolysis of tumor cells, immune reaction against released tumor antigens and local chemotherapy. Methods: Prior to initiating clinical development, the anti-tumor activity of the TG6002/5-FC combination was investigated, using U-87MG human GBM cell line and patient-derived cell line...