title: A human neutralizing antibody specific to Ang-2 inhibits ocular angiogenesis.
abstract: OBJECTIVE
  Angiogenesis, a critical contributor to ocular as well as neoplastic diseases, is stimulated by endothelial production of angiopoietin-2 (Ang2). Our objective was to determine the requirement of ocular angiogenesis for Ang2 in animal models of disease.
  
  
  METHODS
  We developed and compared the effect of a novel human Ang2 antibody with a pan-angiopoietin strategy on angiogenesis in ocular angiogenesis in animal models of oxygen-induced retinopathy, and laser photocoagulation and confirmed its efficacy in xenografted human colorectal tumors.
  
  
  RESULTS
  Human anti-Ang2 and anti-angiopoietin1(Ang1)/Ang2 antibodies blocked colorectal carcinoma growth in immuno-compromised mice (p < 0.001, n = 6). Injection of 1 μg of Ang2 or Ang2/Ang1 antibody-inhibited angiogenesis in models of retinal (p < 0.001, n = 6), and choroidal neovascularization (p < 0.001, n = 11-13 per group) to levels similar to that with anti-VEGF antibodies. There was no difference between Ang2 specific and Ang1/Ang2 bi-specific antibodies. In vitro, Ang2 antibodies showed no cytotoxicity and did not inhibit endothelial cell migration or proliferation.
  
  
  CONCLUSIONS
  Thus, human Ang2 antibodies are potentially therapeutic agents for ocular neovascularization in models of retinal and choroidal neovascularization, in the absence of VEGF inhibition.
authors.affiliation: Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, Veterinary Sciences Building, University of Bristol, Bristol, UK.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Rennel
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Regula
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Harper
authors.forename: Markus
authors.initials: M
authors.lastname: Thomas
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: David O
authors.initials: DO
authors.lastname: Bates
mesh_terms: D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous
chemical_list: D042702:Angiopoietin-2; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; C099439:Ang2 protein, mouse; D012259:Ribonuclease, Pancreatic