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 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.