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Potent anti-angiogenesis and anti-tumor activity of a novel human anti-VEGF antibody, MIL60

Cellular & Molecular Immunology volume 11, pages 285–293 (2014)Cite this article

Abstract

Angiogenesis is crucial for tumor development, growth and metastasis. Vascular endothelial growth factor (VEGF) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEGF can starve tumors. Avastin, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. However, the price of Avastin is extremely high for Chinese people. Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin (the KD value of MIL60 was 44.5 pM, while that of Avastin was 42.7 pM). MIL60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation (the IC50 value of MIL60 was 31±6.4 ng/ml and that of Avastin was 47±8.1 ng/ml), migration (8 µg/ml or 0.8 µg/ml MIL60 versus the control: P<0.05) and tube formation (2 µg/ml or 0.2 µg/ml MIL60 versus the control: P<0.05) via the VEGFR2 signaling pathway. Moreover, MIL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistry analysis (MIL60 versus N.S.: P=0.0007; Avastin versus N.S.: P=0.00046). These data suggest that MIL60 is a potential therapeutic, anti-angiogenic agent. Our work provides a novel anti-VEGF antibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.

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Acknowledgements

This work was supported by grants from the National Sciences Fund (Nos. 31370938 and 81272528) and the National High Technology Research and Development Program (863 Program, No. 2012AA02A302).

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Author notes

  1. Jing Yang, Qun Wang and Chunxia Qiao: These authors contributed equally to this work.

  2. Dr M Lv, Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing 100850, China. E-mail: lm62033@aliyun.com

  3. Dr JN Feng, Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing 100850, China. E-mail: Fengjiannan1970@qq.com

Authors and Affiliations

  1. Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China

    Jing Yang, Chunxia Qiao, Zhou Lin, Xinying Li, Tingting Zhou, Yan Li, Beifen Shen, Ming Lv & Jiannan Feng

  2. Department of Pathogens and Immunology, Logistics College of Chinese People's Armed Police Forces, Tianjin, China

    Jing Yang

  3. Department of Ophthalmology, General Hospital of People's Liberation Army, Beijing, China

    Qun Wang & Yifei Huang

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  1. Jing Yang
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Supplementary Information accompanies the paper on Cellular & Molecular Immunology's website. (http://www.nature.com/cmi).

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Yang, J., Wang, Q., Qiao, C. et al. Potent anti-angiogenesis and anti-tumor activity of a novel human anti-VEGF antibody, MIL60. Cell Mol Immunol 11, 285–293 (2014). https://doi.org/10.1038/cmi.2014.6

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