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Updated: Mar 26, 2026
Construction of Synthetic Phage Displayed Fab Library with Tailored Diversity
Published on: May 1, 2018
Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library
Yan-Da Lai1, Yen-Yu Wu2, Yi-Jiue Tsai3
1Department of Protein Engineering, Development Center for Biotechnology, New Taipei City 22180, Taiwan. alienwhale@yahoo.com.tw.
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.
Insights
Researchers developed novel antibodies targeting vascular endothelial growth factor (VEGF) to combat solid tumors. Three new antibodies demonstrated superior tumor growth inhibition compared to Avastin in preclinical models.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Vascular endothelial growth factor (VEGF) drives angiogenesis, crucial for solid tumor growth and metastasis.
- Blocking VEGF is a validated therapeutic strategy, with antibodies like Avastin approved for clinical use.
- There is a need for novel VEGF-targeting antibodies with enhanced tumor regression capabilities.
Purpose of the Study:
- To systematically generate and select novel antibodies recognizing VEGF.
- To identify antibodies with superior tumor regression potential compared to existing therapies.
- To evaluate the efficacy of selected antibodies in preclinical cancer models.
Main Methods:
- Generation of three phage display libraries (scFv-M13KO7, Fab-M13KO7, scFv-Hyperphage) using recombinant human VEGF.
- Application of solid-phase and solution-phase panning strategies across libraries, yielding 64 VEGF-recognizing antibodies.
- Selection of eight antibodies based on epitope mapping, binding affinity, and in vitro tumor inhibition for in vivo evaluation.
Main Results:
- Three selected antibodies demonstrated improved inhibition of tumor growth in a human COLO 205 xenograft model.
- Tumor growth ratios ranged from 328%-347% for the top antibodies, compared to 435% for Avastin at Day 21.
- These results indicate enhanced anti-tumor efficacy of the novel antibodies over the current standard.
Conclusions:
- The study successfully identified three novel antibodies targeting VEGF with enhanced tumor regression abilities.
- These antibodies represent promising candidates for further development in VEGF-targeted cancer therapy.
- The findings support the potential of these antibodies to improve upon existing therapeutic strategies.
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