Tissue inhibitor of metalloproteinases (timp) linked to...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 19/00 (2006.01) A61K 38/57 (2006.01) C07K 14/81 (2006.01) C12N 15/62 (2006.01)

Patent

CA 2622042

The present invention relates to fusion constructs of glycosylphosphatidylinositol (GPI)- anchored tissue inhibitors of metalloproteinases (TIMPs) and their use for the treatment of cancer and in regenerative medicine. By this approach, the GPI-anchored TIMP proteins are incorporated into the surface membrane of tumor cells and render tumor cells sensitive to FAS-induced apoptosis. Furthermore, the fusion constructs of the present invention are effective agents useful in wound healing applications. In one embodiment, the TIMP is linked to mucin followed by GPI in order to enhance surface presentation. The use of GPI to link TIMP renders the resulting fusion protein particularly useful as an anti-cancer agent for the treatment of cancer, and, in particular, any residual cancer following an incomplete surgical resection of primary tumors in an individual.

L'invention concerne des constructions, obtenues par fusion, d'inhibiteurs tissulaires de métalloprotéinases (TIMP) à ancrage glycosylphosphatidylinositol (GPI), ainsi que leur utilisation pour traiter le cancer, et en médecine régénératrice. Selon l'invention, les protéines TIMP à ancrage GPI sont incorporées dans la membrane de surface de cellules tumorales, et rendent ces cellules tumorales sensibles à une apoptose induite par FAS. En outre, les constructions de fusion selon l'invention constituent des agents efficaces pouvant être utilisés dans des applications de guérison de plaie. Dans un mode de réalisation de cette invention, la protéine TIMP est liée à une mucine, puis une ancre GPI pour améliorer la présentation en surface. L'utilisation de GPI pour relier la protéine TIMP permet de former des protéines de fusion pouvant en particulier être utilisées en tant qu'agents anticancéreux pour traiter le cancer, et notamment tout cancer résiduel à la suite d'une résection chirurgicale incomplète de tumeurs primaires chez un individu.

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