BioWorld International Correspondent

PARIS - Gene therapy company Transgene SA has decided to initiate clinical development of a new cancer therapy, MVA-FCU1, and plans to embark on a Phase I trial in the second half of 2004.

The mechanism of action of MVA-FCU1 entails converting a nontoxic prodrug into a compound that is toxic for cancer cells, creating, in effect, a localized chemotherapy within the tumor.

The product uses a highly attenuated vaccinia virus vector to deliver Transgene's patented FCU1 gene. The gene was obtained by combining the desaminase cytosine gene with that of the phosphoribosyltransferase uracil of Saccharomyces cerevisiae. FCU1 codes for a chimerical protein that transforms the nontoxic 5-FC compound into the chemotherapy product 5-FU, which has long been known for its efficacy.

MVA-FCU1 is administered by intratumoral injection in conjunction with the oral administration of 5-FC. In preclinical studies it was found to deliver a concentration of 5-FU in treated tumors that was 20 times greater than that obtained through conventional 5-FU chemotherapy, and without any trace of 5-FU in the blood circulation system. In addition, 5-FC was found to have been transformed into 5-FU within the tumor for at least two weeks after the administration of MVA-FCU1. Moreover, the product successfully checked tumor growth in in vivo models of highly aggressive colon tumors.

MVA-FCU1 is Transgene's third therapeutic approach to the treatment of cancer, in addition to its anticancer vaccines and immunotherapy products. In preparation for the clinical trial, which will be in patients suffering from metastatic colorectal cancer with inoperable hepatic metastases, the company will produce clinical batches of MVA-FCU1 at its production facility in Strasbourg and submit them for regulatory toxicity tests.