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Centre National De La Recherche Scientifique

Institut Gustave Roussy

Gencell Sas

Thierry Ragot

Michel Perricaudet

Patrice Yeh

Jeannette Soria

Claudine Soria

Hedi Mohamed Haddada

Yves Legrand

He Lu

Paule Opolon

Frank Griscelli

Hong Li

Hédi Mohamed Haddada

Christelle Mabilat

A recombinant nucleic acid used for the production of a defective adenovirus containing an inserted sequence coding for a cytokine under the control of a promoter in the genomic sequence of the recombinant adenovirus. This recombinant adenovirus is useful in the preparation of anti-tumoral drugs which can be directly injected into the tumor of the host.

Defective recombinant adenoviruses expressing cytokines for antitumor treatment

The present invention relates to gene therapy for the treatment of tumors. The invention more particularly relates to introduction of a gene encoding an anti-angiogenic factor into cells of a tumor, for example with a defective adenovirus vector, to inhibit growth or metastasis, or both, of the tumor. In a specific embodiment, delivery of a defective adenovirus that expresses the amino terminal fragment of urokinase (ATF) inhibited growth and metastasis of tumors. These effects were correlated with a remarkable inhibition of neovascularization within, and at the immediate vicinity of, the injection site. Delivery of a defective adenovirus vector that expresses kringles 1 to 3 of angiostatin inhibited tumor growth and tumorigenicity, and induced apoptosis of tumor cells. The invention further provides viral vectors for use in the methods of the invention.

Adenovirus-mediated intratumoral delivery of an angiogenesis antagonist for the treatment of tumors

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Meudon, France

Thierry Ragot