Compositions and methods for modulating vascular development

Abstract

The present invention provides methods of using EGFL7 antagonist to modulate vascular development. Also provided herein are methods of screening for modulators of EGFL7 activity. Furthermore, methods of treatment using EGFL7 antagonists are provided.

1 . A method of reducing or inhibiting angiogenesis in a subject having a pathological condition associated with angiogenesis, comprising administering to the subject an EGFL7 antagonist capable of interfering with EGFL7-induced endothelial cell migration, thereby reducing or inhibiting angiogenesis in the subject.  
     
     
         2 . The method of  claim 1 , wherein the EGFL7 antagonist is an anti-EGFL7 antibody.  
     
     
         3 . The method of  claim 1 , wherein the pathological condition is a neoplasm.  
     
     
         4 . The method of  claim 3 , wherein the neoplasm is a carcinoma.  
     
     
         5 . The method of  claim 1 , wherein the pathological condition is associated with the eye.  
     
     
         6 . The method of  claim 5 , wherein the pathological condition is an intraocular neovascular disease.  
     
     
         7 . The method of  claim 1 , further comprising administering to the subject an anti-angiogenic agent.  
     
     
         8 . The method of  claim 7 , wherein the anti-angiogenic agent is administered prior to or subsequent to the administration of the EGFL7 antagonist.  
     
     
         9 . The method of  claim 7 , wherein the anti-angiogenic agent is administered concurrently with the EGFL7 antagonist.  
     
     
         10 . The method of  claim 7 , wherein the anti-angiogenic agent is an antagonist of vascular endothelial cell growth factor (VEGF).  
     
     
         11 . The method of  claim 10 , wherein the VEGF antagonist is an anti-VEGF antibody.  
     
     
         12 . The method of  claim 11 , wherein the anti-VEGF antibody is bevacizumab.  
     
     
         13 . The method of  claim 1 , wherein the EGFL7 antagonist's ability to interfere with EGFL7-induced endothelial cell migration is detected in an in vitro cell migration assay.  
     
     
         14 . A method of enhancing efficacy of an anti-angiogenic agent in a subject having a pathological condition associated with angiogenesis, comprising administering to the subject an EGFL7 antagonist in combination with the anti-angiogenic agent capable of inhibiting angiogenesis, thereby enhancing said anti-angiogenic agent's inhibitory activity.  
     
     
         15 . The method of  claim 14 , wherein the EGFL7 antagonist is an anti-EGFL7 antibody.  
     
     
         16 . The method of  claim 14 , wherein the pathological condition is a neoplasm.  
     
     
         17 . The method of  claim 16 , wherein the neoplasm is a carcinoma.  
     
     
         18 . The method of  claim 14 , wherein the pathological condition is associated with the eye.  
     
     
         19 . The method of  claim 18 , wherein the pathological condition is an intraocular neovascular disease.  
     
     
         20 . The method of  claim 17 , further comprising administering a chemotherapeutic agent.