Chemokine-mucin fusions linked to...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 14/52 (2006.01) A61K 38/19 (2006.01) C07K 14/47 (2006.01) C12N 15/62 (2006.01)

Patent

CA 2631587

The present invention relates to chemokine-mucin fusions linked to glycosylphosphatidylinositol (GPI)-anchors and their use as anti-cancer adjuvants and as agents in tissue regeneration and suppression of vascular damage. GPI-linked chemokines are incorporated in the surface membrane of tumour cells and effect a recruitment of cytotoxic immune cells to the tumour site following injection in vivo. Leukocytes, cytotoxic T-cells and NK cells target the chemokine-GPI-anchored tumour cells and modulate cell-mediated lysis of the tumour cells. The efficiency of GPI-anchoring and modulation of immune cells can be further enhanced by linking the chemokine to a mucin domain followed by the GPI-anchor. The GPI-anchored chemokines, with or without mucin domain, are remarkably useful for the inhibition of tumour growth, tissue regeneration, and suppression of acute vascular damage to allografts.

La présente invention concerne des couples chimiokines-mucines liés à des ancrages glycosylphosphatidylinositol (GPI) et leur utilisation en tant qu'adjuvants antinéoplasiques et en tant qu'agents permettant la régénération tissulaire et la suppression d'une lésion vasculaire. Les chimiokines liées à GPI sont incorporées dans la membrane superficielle de cellules tumorales et déclenchent un déplacement des cellules immunes cytotoxiques vers le site de la tumeur après injection in vivo. Les leukocytes, les lymphocytes T cytotoxiques et des cellules NK ciblent les cellules tumorales contenant les chimiokines liées à GPI et ils modulent la lyse cellulaire des cellules tumorales. L'efficacité de l'ancrage GPI et la modulation des cellules immunes peuvent être encore améliorées par liaison des chimiokines à un domaine mucine suivie de l'ancrage GPI. Les chimiokines liées à GPI, qu'elles comprennent ou non un domaine mucine, sont particulièrement utiles au blocage de la croissance tumorale, à la régénération tissulaire et à la suppression de lésions vasculaires importantes sur des allogreffes.

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