Attenuation of tumor growth, metastasis and angiogenesis by...

A - Human Necessities – 61 – K

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A61K 38/51 (2006.01) A61K 38/46 (2006.01) A61P 35/00 (2006.01) A61P 37/00 (2006.01)

Patent

CA 2414185

A highly purified and specific glycosaminoglycan degrading enzyme, chondroitinase AC, and to a lesser extent, chondroitinase B, can be used in the treatment of metastatic cancers and in other disorders characterized by angiogenesis. The enzymatic removal of chondroitin sulfates A and C, and to a lesser extent, chondroitin sulfate B, from cell surfaces directly decreases the ability of tumor cells to invade blood vessels and thus prevents the formation of metastatic, or secondary tumors; inhibits tumor cell growth; and decreases angiogenesis by inhibiting both endothelial cell proliferation and capillary formation. Decreasing the formation of new blood vessels into the tumor in turn decreases the potential for tumor growth, and further decreases the ability of tumor cells to invade the bloodstream. These effects are opposite to the pro-metastatic effects of tumor-secreted heparanase.

Selon l'invention, une enzyme spécifique très purifiée dégradant le glycosaminoglycane, la chondroïtinase AC, et dans une moindre mesure la chondroïtinase B peuvent être utilisées dans le traitement de cancers métastatiques et d'autres maladies liées à l'angiogenèse. L'extraction enzymatique de sulfates de chondroïtine A et C, et dans une moindre mesure de sulfate de chondroïtine B de la surface cellulaire, permet de diminuer directement la capacité de cellules tumorales à envahir les vaisseaux sanguins, et d'empêcher par conséquent la formation de tumeurs métastatiques ou secondaires, d'inhiber la croissance de cellules tumorales, et de diminuer l'angiogenèse par inhibition de la prolifération des cellules endothéliales et de la formation de capillaires. La réduction de la formation de nouveaux vaisseaux sanguins dans la tumeur permet de diminuer le potentiel de croissance tumorale, et de diminuer la capacité de cellules tumorales à envahir le flux sanguin. Ces effets sont opposés aux effets pro-métastatiques de l'héparanase sécrétée par les tumeurs.

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