Adenovirus-mediated intratumoral delivery of an angiogenesis...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/57 (2006.01) A61K 38/48 (2006.01) A61K 38/49 (2006.01) A61K 48/00 (2006.01) C12N 15/58 (2006.01)

Patent

CA 2288306

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.

La présente invention concerne l'utilisation de thérapie génique dans le traitement de tumeurs et notamment l'introduction d'un gène codant un facteur antiangiogénique dans des cellules d'une tumeur, par exemple, au moyen d'un vecteur adénoviral défectif, afin d'inhiber la croissance ou la métastase, ou les deux, de la tumeur. Dans un mode de réalisation spécifique, l'apport d'un adénovirus défectif exprimant le fragment aminé terminal de l'urokinase (ATF) a inhibé la croissance et la métastase de tumeurs. Ces effets sont en corrélation avec une inhibition remarquable de la néoformation de vaisseaux sanguins dans le site d'injection et au voisinage immédiat de celui-ci. L'apport d'un vecteur adénoviral défectif exprimant les kringles 1 à 3 de l'angiostatine a inhibé la croissance tumorale et l'action tumorigène et induit l'apoptose de cellules tumorales. L'invention concerne en outre des vecteurs viraux, utiles dans les procédés ci-dessus.

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