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The efficacy of a high affinity humanized anti-Vascular Endothelial Growth Factor fusion protein，KH902，suppression on the experimental choroidal neovasularization in monkeys |
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| The efficacy of a high affinity humanized anti-Vascular Endothelial Growth Factor fusion protein，KH902，suppression on the experimental choroidal neovasularization in monkeys |
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作者：Ming Zha… 文章来源：Dept. of Ophthalmology, West China Hospital, Sichuan University, China. 610041; 点击数：847 更新时间：2007/5/31 8:50:44 
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| Purpose: To evaluated the binding affinity with vascular endothelial growth factor and the efficacy of humanized fusion protein, KH902, in suppression on the experimental choroidal neovascularization of rhesus monkey. Method: The binding affinity with VEGF was measured by using human VEGF ELISA kit. The experimental CNV was induced by perimacular laser injury in eyes of rhesus monkeys and confirmed by fluorescence fundus angiography and optical coherence tomography on days 21 after laser treatment. Then, the monkeys were divided into treatment group and control group. The eyes of treatment group were received introvitreal injection of KH902 (Dose: 0.1mg, 0.3mg and 0.5mg, each dose contain 4 eyes) and the eyss of control group were received phosphate buffer injection by the same procedure. Monkeys were observed 4 weeks after injection by ophthalmic examination, fluorescence fundus angiography, optical coherence tomography, histopathology and Immunohistochemistry Analysis. Result: KH902 presents high affinity with VEGF and the mean of IC50 is 10 pM. In the eyes of treatment group which received 0.3mg and 0.5mg KH902 introvitreal injection, the choroidal neovascularization leakage was obviously decrease than that before injection and no leakage was observed at the end of observation after injection. No fiber-vasculosa membrane were detected by OCT and histopathologic observation. In the 0.1mg KH902-treated and control eyes, the choroidal neovascularization leakage was still exist. Rupture of Bruch’s membrane and flat dome-like cell proliferation under sensory retina could be seen. Proliferating cells consist mainly of immature vascular endothelial cells that stained by CD34 and CD105 and less-pigmented, spindle-shaped RPE cells. The reduction of experimental CNV was greater in 0.3mg and 0.5mg treated eyes than that in 0.1mg treated eyes and the eyes of control group. The result of mf-ERG demonstrated the improvement better in 0.3mg and 0.5mg KH902-treated eyes than that in 0.1mg KH902-treated and control eyes simultaneously. Conclusion: KH902 present high affinity with VEGF. Single 0.3mg or 0.5mg KH902 intravitreal injection effectively inhibited leakage and growth of the CNV in rhesus monkeys without evidence of toxicity. This study suggests that KH902 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of KH902 in therapy for human CNV associated with age-related macular degeneration.
Key Words: Vascular endothelial growth factor, Choroidal neovascularization, Age-related macular degeneration, fusion protein, intravitreal injection
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