Angiogenesis is a complex process involving the proliferation, migration, and precise three dimensional alignment of endothelial cells. A wide range of disease processes including solid tumor growth, diabetic retinopathy, inflammatory arthritis, and psoriasis are associated with aberrant angiogenesis. If relatively non-toxic agents were available to inhibit angiogenesis specifically; management of these """"""""angiogenic diseases"""""""" could be greatly improved. The applicant has shown in previous investigations that recombinant human platelet factor four (rPF4) interferes with several steps in the neovascularization process and inhibits angiogenesis in vivo. If injected directly into solid tumors in several murine models rPF4 inhibits tumor growth, probably by inhibiting tumor neovascularization. The short serum half-life of rPF4, however, limits its systemic utility. Conjugation of several therapeutically useful proteins to polyethylene glycol (PEG) have been shown to extend their serum half-lives while maintaining biological activity. It is anticipated that conjugation of rPF4 to PEG will extend the circulation half-life of this protein and may yield a useful, systemically administered angiostatic agent.
