Chemokine-mucin fusions linked to glycosylphosphatidylinositol (GPI)-anchors in tissue regeneration and as tumour immune adjuvants

摘要

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