Treating macular degeneration using antibodies to aminophospholipids
Disclosed are the surprising discoveries that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are stable and specific markers accessible on the luminal surface of tumor blood vessels, and that the administration of an anti-aminophospholipid antibody alone is sufficient to induce thrombosis, tumor necrosis and tumor regression in vivo. This invention therefore provides anti-aminophospholipid antibody-based methods and compositions for use in the specific destruction of tumor blood vessels and in the treatment of solid tumors. Although various antibody conjugates and combinations are thus provided, the use of naked, or unconjugated, anti-phosphatidylserine antibodies is a particularly important aspect of the invention, due to simplicity and effectiveness of the approach.
1. A method for treating an animal having a vasculature-associated disease having, as a component of the disease, prothrombotic blood vessels, said method comprising administering to said animal an amount of at least a first isolated or purified antibody effective to treat said disease; wherein said at least a first isolated or purified antibody binds to phosphatidylserine or a phosphatidylserine-protein complex in said disease; wherein said disease is macular degeneration; and wherein said at least a first isolated or purified antibody comprises a function of binding to phosphatidylserine or a phosphatidylserine-protein complex on the luminal surface of vascular endothelial cells of blood vessels of a vascularized tumor when administered to an animal having a vascularized tumor.
2. The method of claim 1 , wherein said at least a first isolated or purified antibody binds to phosphatidylserine in said disease and comprises a function of binding to phosphatidylserine on the luminal surface of vascular endothelial cells of blood vessels of a vascularized tumor when administered to an animal having a vascularized tumor.
3. The method of claim 1 , wherein said at least a first isolated or purified antibody binds to a phosphatidylserine-protein complex in said disease and comprises a function of binding to a phosphatidylserine-protein complex on the luminal surface of vascular endothelial cells of blood vessels of a vascularized tumor when administered to an animal having a vascularized tumor.
4. The method of claim 3 , wherein said at least a first isolated or purified antibody binds to a phosphatidylserine-β 2 -glycoprotein I complex in said disease and comprises a function of binding to a phosphatidylserine-β 2 -glycoprotein I complex on the luminal surface of vascular endothelial cells of blood vessels of a vascularized tumor when administered to an animal having a vascularized tumor.
5. The method of claim 1 , wherein said at least a first isolated or purified antibody is at least a first IgG or IgM antibody.
6. The method of claim 1 , wherein said at least a first isolated or purified antibody is at least a first human, humanized or part-human chimeric antibody.
7. The method of claim 6 , wherein said at least a first isolated or purified antibody is a chimeric antibody that comprises mouse antibody variable region domains that bind to said phosphatidylserine or phosphatidylserine-protein complex and wherein said mouse antibody variable region domains are attached to a human antibody constant region.
8. The method of claim 1 , wherein said at least a first isolated or purified antibody is at least a first dimer, trimer or multimer of said antibody.
9. The method of claim 1 , wherein said at least a first isolated or purified antibody is at least a first monoclonal antibody.
10. The method of claim 1 , wherein said at least a first isolated or purified antibody is administered to said animal by intravenous administration.
11. The method of claim 1 , wherein said method is part of a combined treatment method for said disease.
12. The method of claim 11 , wherein said combined treatment method for said disease comprises radiotherapy.
13. The method of claim 11 , wherein said combined treatment method for said disease comprises administration of an anti-angiogenic agent.
14. The method of claim 1 , wherein said at least a first isolated or purified antibody is at least a first recombinant antibody.
15. The method of claim 1 , wherein said at least a first isolated or purified antibody is at least a first bispecific antibody.
16. The method of claim 1 , wherein said at least a first isolated or purified antibody is administered to said animal by direct instillation into the disease site.