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AssigneeGenCell Corporation
InventorsHong Li, He Lu, Frank Griscelli, Paule Opolon, Claudine Soria, Thierry Ragot, Yves Legrand, Jeannette Soria, Christelle Mabilat, Michel Perricaudet, Patrice Yeh
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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.
A method for inhibiting the growth or metastasis or both of a tumor comprising introducing a vector into the tumor, the vector comprising a nucleic acid sequence encoding an amino terminal fragment of urokinase that comprises an EGF-like domain, with the exception that the nucleic acid sequence does not encode full length urokinase, wherein the nucleic acid sequence is operably associated with an expression control sequence that provides for expression in a cell of the tumor.
A method for inhibiting the growth of a tumor comprising introducing into the tumor a defective adenovirus vector comprising a DNA sequence encoding an anti-angiogenic factor operably associated with an expression control sequence that provides for expression of the anti-angiogenic factor in a cell of the tumor, wherein the anti-angiogenic factor comprises an amino terminal fragment of urokinase that comprises an EGF-like domain, with the exception that the anti-angiogenic factor is not full length urokinase.
A defective adenovirus vector comprising a gene encoding an anti-angiogenic factor operably associated with an expression control sequence, wherein the anti-angiogenic factor comprises an amino terminal fragment of urokinase comprising an EGF-like domain, with the exception that the anti-angiogenic factor is not full length urokinase.
Dependencies are inferred from the claim text.