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The Pharmacology Study of a New Recombinant Human VEGF Receptor-Fc Fusion Protein on Experimental Choroidal Neovascularization

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Abstract

Purpose

KH902, a recombinant fusion protein, is designed for treatment of neovascular age-related macular degeneration. The study is to investigate the prevention efficacy of KH902 on experimental choroidal neovascularization (CNV) in a monkey model.

Materials and Methods

Binding assay and endothelial cell proliferation assay were used to evaluate activity and bioactivity of KH902 in vitro while an initial comparison of bioactivity was made between KH902 and Ranizumab (Lucentis). Ocular and systemic levels of KH902 were analyzed by enzyme-linked immunosorbent assay (ELISA) method after single intravitreal administration to evaluate its availability to ocular fundus. In vivo pharmacological study, CNV was induced by laser in monkeys and KH902 prevention efficacy on CNV was evaluated by incidence of CNV and several ophthalmic examinations.

Results

KH902 is a unique fusion protein with high affinity to VEGF and good availability to target tissue, beneficial to good bioactivity in vivo. In vivo pharmacological study, the incidence of CNV formation was largely reduced in KH902 treatment groups. Furthermore, the leakage of CNV in control group which crossed over to KH902 treatment 40 days after laser was much less than that before KH902 treatment.

Conclusion

KH902 was effective to prevent the formation of experimental CNV and also to treat pre-existed CNV without evidence of toxicity. This study suggests that KH902 has promise as a local anti-angiogenic treatment of CNV-related diseases.

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Abbreviations

AMD:

age-related macular degeneration

CNV:

choroidal neovascularization; HUVEC

OCT:

optical coherent tomography

VEGF:

vascular endothelial growth factor

HUVEC:

human umbilical vein endothelial cell

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Acknowledgements

The authors would like to thank Bin Liu and his colleagues of the National Chengdu Center for Safety Evaluation of Drugs for they provide and administrate the experimental monkeys.

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Authors and Affiliations

  1. Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China

    Ming Zhang & Qingjie Xia

  2. Chengdu Kanghong Biotechnology Co. Inc., 36 ShuXi Road, JinNiu Distriction, Chengdu, Sichuan Province, 610036, China

    Dechao Yu, Chun Yang & Hong Li

  3. State Chengdu Traditional Chinese Medicine Safety Evaluation Center, Chengdu, Sichuan, 610041, China

    Wang Li & Bin Liu

Authors
  1. Ming Zhang
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  2. Dechao Yu
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  3. Chun Yang
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  4. Qingjie Xia
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  5. Wang Li
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  6. Bin Liu
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  7. Hong Li
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Correspondence to Hong Li.

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Zhang, M., Yu, D., Yang, C. et al. The Pharmacology Study of a New Recombinant Human VEGF Receptor-Fc Fusion Protein on Experimental Choroidal Neovascularization. Pharm Res 26, 204–210 (2009). https://doi.org/10.1007/s11095-008-9718-9

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  • DOI: https://doi.org/10.1007/s11095-008-9718-9

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