METHOD FOR INHIBITING PLATELET DERIVED GROWTH FACTOR SIGNALING WITH C3aR OR C5aR ANTIBODIES

Abstract

A method of modulating growth factor responses of cells expressing C3a receptor (C3aR) and C5a receptor (C5aR) and at least one growth factor receptor includes administering to the cells at least one agent that modulates C3aR and/or C5aR signaling of the cells.

Having described the invention, we claim: 
     
         1 . A method of modulating growth factor responses of cells expressing C3a receptor (C3aR) and C5a receptor (C5aR) and at least one growth factor receptor, the method comprising:
 administering to the cells at least one agent that modulates C3aR and/or C5aR signaling of the cells.   
     
     
         2 . The method of  claim 1 , the agent being selected from the group consisting of a complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and C5a receptor (C5aR), a STATS/IL-6 signalling pathway antagonist, a thrombin inhibitor, and a combination thereof, the agent being administered to the cells at an amount effective to inhibit at least one of growth, viability, or mitosis of the cells. 
     
     
         3 . The method of  claim 1 , the agent being selected from the group consisting of a STATS inhibitor, an IL-6 inhibitor, a thrombin inhibitor, and a combination thereof, the agent being administered to the cells at an amount effective to inhibit at least one of growth, viability, or mitosis of the cells. 
     
     
         4 . The method of  claim 2 , the complement antagonist comprising at least one of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR. 
     
     
         5 . The method of  claim 2 , the cells comprising at least one of smooth muscle cells, endothelial cells, leukocytes, cancer cells, neural cells, or fibroblasts and the agent inhibiting at least one growth, viability, or mitosis of the at least one of smooth muscle cells, endothelial cells, leukocytes, cancer cells, neural cells, or fibroblasts in response to growth factor stimulation. 
     
     
         6 . The method of  claim 5 , the agent comprising the complement antagonist and cells being in vasculature of the subject, proximate or about the periphery of a vascular injury, and the agent being administered to the subject to inhibit at least one of growth, viability, or mitosis of the cells following growth factor stimulation of the cells. 
     
     
         7 . The method of  claim 6 , wherein the complement antagonist inhibits at least one of atherogenesis, thrombosis, restinosis, or neointimal formation in the subject. 
     
     
         8 . The method of  claim 7 , the complement antagonist comprising at least one of DAF or an antibody directed against at least one of C3, C5, C3 convertase, C5 convertase, C3a, C5a, C3aR, or C5aR 
     
     
         9 . The method of  claim 5 , the cells comprising cancer cells and the agent being selected from the group consisting of a STAT3 inhibitor, an IL-6 inhibitor, a thrombin inhibitor and a combination thereof, the agent being administered to the cells at an amount effective to inhibit at least one growth, viability, or mitosis of the cells. 
     
     
         10 . The method of  claim 5 , the cells comprising endothelial cells and the agent being selected from the group consisting of a STAT3 inhibitor, an IL-6 inhibitor, a thrombin inhibitor and a combination thereof, the agent being administered to the endothelial cells at an amount effective to inhibit at least one growth, viability, or mitosis of the cells. 
     
     
         11 . A method of inhibiting neointimal formation in the vasculature of a subject as a result of a vascular injury, the method comprising:
 administering to at least one of endothelial cells or smooth muscle cells at the site of or proximate the site of the injured vasculature an agent that inhibits C3aR and/or C5aR signaling of the cells, the agent including a complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and C5a receptor (C5aR).   
     
     
         12 . The method of  claim 11 , the agent being administered at an amount effect to inhibit at least one of PDGF production by the cells, cell growth, cell viability, or cell mitosis. 
     
     
         13 . The method of  claim 11 , wherein the agent is administered at an amount effective to inhibit at least one of atherogenesis, thrombosis, or restinosis of the subject. 
     
     
         14 . The method of  claim 11 , the agent being provided on an endovascular device and the endovascular device being administered to the site of vascular injury. 
     
     
         15 . The method of  claim 14 , the endovascular device comprising at least one of stents, drug delivery catheters, grafts, and drug delivery balloons utilized in the vasculature of a subject. 
     
     
         16 . A method of inhibiting aberrant angiogenesis and/or vasculogenesis in tissue of a subject, the method comprising:
 administering to the tissue of the subject at least one agent that inhibits at least one of C3a or C5a signaling in endothelial cells of the tissue, the agent being selected from the group consisting of a STATS inhibitor, an IL-6 inhibitor, a thrombin inhibitor and a combination thereof.   
     
     
         17 . The method of  claim 16 , the tissue comprising tumor tissue and the agent being administered at an amount effect to inhibit aberrant tumor growth. 
     
     
         18 . The method of  claim 16 , the tissue comprising choroid tissue and the agent being administered at an amount effective to treat age-related macular degeneration. 
     
     
         19 . The method of  claim 16 , further comprising administering to the tissue a complement antagonist that substantially reduces the interaction of at least one of C3a or C5a with the C3a receptor (C3aR) and C5a receptor (C5aR).