PARIS - Génopoiétic, a Paris-based gene therapy company set up in 1994 to develop therapies for glioblastoma and liver and skin cancers, has successfully applied its technology in an animal model for the treatment of breast cancer. Clinical trials on women suffering from metastatic breast cancer are due to get under way in a few months.

The therapy involves a combination of genetic manipulation and conventional medicinal treatment. To start, the so-called “suicide gene“ HSV1-tk, which is the thymidine-kinase gene of the herpes simplex virus, is injected into the tumor cells by means of a genetically modified retrovirus. The antiviral Cymevene (ganciclovir), commonly used for treating herpetic infections, is then administered. The result is the selective destruction of tumor cells by apoptosis, or programmed cell death.

Tests of the therapy have been carried out using an experimental breast cancer model in rats, which the researchers claim is very similar to human breast cancer. They also emphasize that the therapy is effective not only against the lesion targeted, but also against metastases removed from the main tumor.

The method was developed by a joint team of researchers from both Génopoiétic and university hospitals, headed by David Klatzmann, of La Pitié-Salpêtrière hospital and Pierre-et-Marie-Curie University, in Paris. Klatzmann is a founder of Génopoiétic, along with Jean-Loup Salzmann, of the University of Paris-XIII. The method's main technical processes are covered by patents held by Génopoiétic and Pierre-et-Marie-Curie University.

“This is the first time a gene therapy has been tested on a spontaneous cancer model that is close to human breast cancer,“ Klatzmann said.

The spontaneous induction of cancer resulted in the rats developing between two and six tumors. “In each of the animals, all the tumors, both those treated and those not treated, were reduced by over 90 percent,“ Klatzmann said, adding the mechanisms responsible for this phenomenon are not yet fully understood, but are “certainly immunological in origin.“ A clinical trial on women suffering from metastatic breast cancer is due to begin early in 1999.

The combination therapy originally was developed by Génopoiétic for the treatment of glioblastoma and proved successful in a Phase I clinical trial in 1995 and 1996. That trial helped confirm the validity of gene therapy treatments using the thymidine-kinase gene, and demonstrated the double-whammy effect of combining them with ganciclovir. On the strength of those results, Génopoiétic embarked on a Phase II trial of the therapy on glioblastoma in 1997.

Génopoiétic was founded in 1994 and is one of 17 companies constituting the scientific exchange network of RPR Gencell, the gene and cell therapy division of Rhône-Poulenc Rorer. Rhône-Poulenc Rorer is the pharmaceutical affiliate of the Paris-based Rhône-Poulenc Group.

Génopoiétic has a plant in Lyons, where it produces the genes required for its research, as well as clinical gene sets, master cell banks and GMP-grade cells, viruses, plasmins and recombinant proteins for supply to companies and university laboratories engaged in cell and gene therapy research. *