PARIS  Rhtne-Poulenc Rorer Inc. (RPR), the pharmaceutical affiliate of French chemical giant Rhtne-Poulenc, of Paris, has set up a joint gene therapy laboratory in association with the Institut Gustave-Roussy (IGR), Europe¿s leading cancer clinic, and the National Scientific Research Center (CNRS  Centre National de la Recherche Scientifique). The new laboratory is located at the IGR¿s premises in Villejuif, near Paris.

The unit will conduct research in three main areas: the conception of viral vectors; the study of immune system responses; and the development of applications for treating cancers and genetic diseases of the liver, the muscles (such as muscular dystrophy) and the skin. In particular, it aims to develop more effective adenovirus vectors, especially hybrid vectors enabling the genetic information carried to be maintained in the target cells during successive cellular divisions. A more general objective is to improve the targeting of transferred genes and regulate their expression.

In addition, the unit will explore ways of inhibiting immune system responses, which are a handicap for gene therapy. The first aim is to prevent the proliferation of cytotoxic T cells, which are responsible for the immune system¿s cellular response. Because T cells attack viral proteins and transgenes and eliminate the cells infected, they limit the duration of expression of the transgene. The second goal is to neutralize the production of a cytokine belonging to a family of molecules responsible for the humoral reaction to an adenovirus, which prevents the development of antibodies to it.

As regards cancer therapies, the unit plans to develop a new form of treatment entailing the blocking of tumoral angiogenesis (the irrigation of tumors by blood vessels, which is essential for tumor growth and the propagation of metastases). The approach entails inhibiting the action of enzymes involved in the formation of blood vessels  urokinase and plasminogen  through the use of derived fragments (ATF and angiostatins).

The three partners have been cooperating in the field of cell and gene therapy since signing a collaboration agreement in December 1993 that covered the use of adenovirus vectors for gene therapy purposes. Rhtne-Poulenc Rorer, of College ville, Pa., is heavily committed to gene therapy research, which accounts for 20 percent of its total research and development spending and employs more than 300 researchers.

Frangois Meyer, the company¿s director of research, said RPR could have its first gene therapy product on the market by as early as the end of 2000. It is likely to be a cancer therapy developed by RPR¿s gene therapy division, Gencell, which involves the delivery of the p53 tumor suppressor gene by an adenovirus vector. The therapy is in Phase II clinical trials in Europe and the U.S. for a variety of cancers, including head and neck, liver, ovarian, bladder, breast, lung and glioblastoma.

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