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. CONCLUSION: Thus, human Ang2 antibodies are potentially therapeutic agents for ocular neovascularization in models of retinal and choroidal neovascularization, in the absence of VEGF inhibition.
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 humanAng2 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 humancolorectal 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. CONCLUSION: Thus, humanAng2 antibodies are potentially therapeutic agents for ocular neovascularization in models of retinal and choroidal neovascularization, in the absence of VEGF inhibition.
Authors: Christian Klein; Claudio Sustmann; Markus Thomas; Kay Stubenrauch; Rebecca Croasdale; Jürgen Schanzer; Ulrich Brinkmann; Hubert Kettenberger; Jörg T Regula; Wolfgang Schaefer Journal: MAbs Date: 2012-08-27 Impact factor: 5.857
Authors: Zoe L Grant; Lachlan Whitehead; Vickie Hy Wong; Zheng He; Richard Y Yan; Abigail R Miles; Andrew V Benest; David O Bates; Claudia Prahst; Katie Bentley; Bang V Bui; Robert Ca Symons; Leigh Coultas Journal: J Clin Invest Date: 2020-08-03 Impact factor: 14.808
Authors: Melissa V Gammons; Oleg Fedorov; David Ivison; Chunyun Du; Tamsyn Clark; Claire Hopkins; Masatoshi Hagiwara; Andrew D Dick; Russell Cox; Steven J Harper; Jules C Hancox; Stefan Knapp; David O Bates Journal: Invest Ophthalmol Vis Sci Date: 2013-09-05 Impact factor: 4.799
Authors: Moritz Felcht; Robert Luck; Alexander Schering; Philipp Seidel; Kshitij Srivastava; Junhao Hu; Arne Bartol; Yvonne Kienast; Christiane Vettel; Elias K Loos; Simone Kutschera; Susanne Bartels; Sila Appak; Eva Besemfelder; Dorothee Terhardt; Emmanouil Chavakis; Thomas Wieland; Christian Klein; Markus Thomas; Akiyoshi Uemura; Sergij Goerdt; Hellmut G Augustin Journal: J Clin Invest Date: 2012-05-15 Impact factor: 14.808