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Int. J. Mol. Sci. 2016, 17(2), 214; doi:10.3390/ijms17020214

Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library for Cancer Therapy

Department of Protein Engineering, Development Center for Biotechnology, New Taipei City 22180, Taiwan
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Academic Editor: William Chi-shing Cho
Received: 7 December 2015 / Revised: 21 January 2016 / Accepted: 26 January 2016 / Published: 5 February 2016
(This article belongs to the Collection Advances in Molecular Oncology)
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Abstract

Vascular endothelial growth factor (VEGF) is an important stimulator for angiogenesis in solid tumors. Blocking VEGF activity is an effective therapeutic strategy to inhibit tumor growth and metastasis. Avastin, a humanized monoclonal antibody recognizes VEGF, has been approved by the US Food and Drug Administration. To generate potential VEGF-recognizing antibodies with better tumor regression ability than that of Avastin, we have designed a systematic antibody selection plan. From mice immunized with recombinant human VEGF, we generated three phage display libraries, scFv-M13KO7, Fab-M13KO7, and scFv-Hyperphage, in single-chain Fv (scFv) or Fab format, displayed using either M13KO7 helper phage or Hyperphage. Solid-phase and solution-phase selection strategies were then applied to each library, generating six panning combinations. A total of sixty-four antibodies recognizing VEGF were obtained. Based on the results of epitope mapping, binding affinity, and biological functions in tumor inhibition, eight antibodies were chosen to examine their abilities in tumor regression in a mouse xenograft model using human COLO 205 cancer cells. Three of them showed improvement in the inhibition of tumor growth (328%–347% tumor growth ratio (% of Day 0 tumor volume) on Day 21 vs. 435% with Avastin). This finding suggests a potential use of these three antibodies for VEGF-targeted therapy. View Full-Text
Keywords: phage display; single chain Fv antibody fragment (scFv); Fab antibody fragment; angiogenesis; vascular endothelial growth factor (VEGF) phage display; single chain Fv antibody fragment (scFv); Fab antibody fragment; angiogenesis; vascular endothelial growth factor (VEGF)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lai, Y.-D.; Wu, Y.-Y.; Tsai, Y.-J.; Tsai, Y.-S.; Lin, Y.-Y.; Lai, S.-L.; Huang, C.-Y.; Lok, Y.-Y.; Hu, C.-Y.; Lai, J.-S. Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library for Cancer Therapy. Int. J. Mol. Sci. 2016, 17, 214.

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