Microvascular Research Laboratories, Bristol Heart Institute, School of Physiology and Pharmacology, Veterinary Sciences Building, University of Bristol, Bristol, UK.
Microcirculation. 2011 Oct;18(7):598-607. doi: 10.1111/j.1549-8719.2011.00120.x.
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.
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.
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.
Thus, human Ang2 antibodies are potentially therapeutic agents for ocular neovascularization in models of retinal and choroidal neovascularization, in the absence of VEGF inhibition.
血管生成是眼部疾病和肿瘤疾病的关键因素，由内皮细胞产生的血管生成素-2（Ang2）刺激。我们的目的是确定眼部血管生成对疾病动物模型中 Ang2 的需求。
我们开发并比较了一种新型人 Ang2 抗体与泛血管生成素策略对氧诱导的视网膜病变和激光光凝动物模型中血管生成的影响，并证实了其在人结直肠肿瘤异种移植中的疗效。
人抗 Ang2 和抗血管生成素 1（Ang1）/Ang2 抗体抑制免疫缺陷小鼠中的结直肠癌细胞生长（p < 0.001，n = 6）。在视网膜（p < 0.001，n = 6）和脉络膜新生血管化（p < 0.001，n = 11-13/组）模型中，注射 1μg Ang2 或 Ang2/Ang1 抗体可抑制血管生成，达到与抗 VEGF 抗体相似的水平。Ang2 特异性抗体和 Ang1/Ang2 双特异性抗体之间没有差异。在体外，Ang2 抗体没有细胞毒性，也不抑制内皮细胞迁移或增殖。
因此，人 Ang2 抗体是视网膜和脉络膜新生血管化模型中眼部新生血管形成的潜在治疗剂，而不抑制 VEGF。
