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Updated: Apr 23, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
The carboxyl terminus of VEGF-A is a potential target for anti-angiogenic therapy
James G Carter1, Melissa V R Gammons, Gopinath Damodaran
1Microvascular Research Laboratories, School of Physiology and Pharmacology, University of Bristol, Preclinical Veterinary Sciences Building, Southwell Street, Bristol, BS2 8EJ, UK.
Abstract:
Anti-VEGF-A therapy has become a mainstay of treatment for ocular neovascularisation and in cancer; however, their effectiveness is not universal, in some cases only benefiting a minority of patients. Anti-VEGF-A therapies bind and block both pro-angiogenic VEGF-Axxx and the partial agonist VEGF-Axxxb isoforms, but their anti-angiogenic benefit only comes about from targeting the pro-angiogenic isoforms. Therefore, antibodies that exclusively target the pro-angiogenic isoforms may be more effective. To determine whether C-terminal-targeted antibodies could inhibit angiogenesis, we generated a polyclonal antibody to the last nine amino acids of VEGF-A165 and tested it in vitro and in vivo. The exon8a polyclonal antibody (Exon8apab) did not bind VEGF-A165b even at greater than 100-fold excess concentration, and dose dependently inhibited VEGF-A165 induced endothelial migration in vitro at concentrations similar to the VEGF-A antibody fragment ranibizumab. Exon8apab can inhibit tumour growth of LS174t cells implanted in vivo and blood vessel growth in the eye in models of age-related macular degeneration, with equal efficacy to non-selective anti-VEGF-A antibodies. It also showed that it was the VEGF-Axxx levels specifically that were upregulated in plasma from patients with proliferative diabetic retinopathy. These results suggest that VEGF-A165-specific antibodies can be therapeutically useful.
Insights
New antibodies targeting specific pro-angiogenic VEGF-Axxx isoforms show promise for treating conditions like cancer and eye diseases. These targeted therapies may offer improved effectiveness over current broad-spectrum anti-VEGF-A treatments.
Area of Science:
- Ophthalmology
- Oncology
- Molecular Biology
Background:
- Anti-VEGF-A therapy is a standard treatment for ocular neovascularization and cancer.
- Current therapies target both pro-angiogenic and non-pro-angiogenic VEGF-A isoforms, limiting efficacy in some patients.
- Targeting only pro-angiogenic VEGF-A isoforms may enhance therapeutic benefits.
Purpose of the Study:
- To investigate the potential of C-terminal-targeted antibodies to inhibit angiogenesis.
- To generate and test a polyclonal antibody specific to the pro-angiogenic VEGF-A165 isoform.
Main Methods:
- Generated a polyclonal antibody (Exon8apab) targeting the C-terminus of VEGF-A165.
- Tested Exon8apab's binding affinity to VEGF-A165 and VEGF-A165b in vitro.
- Assessed Exon8apab's efficacy in inhibiting endothelial cell migration, tumor growth, and ocular angiogenesis in vivo.
Main Results:
- Exon8apab selectively targeted VEGF-A165 without binding VEGF-A165b.
- Exon8apab inhibited VEGF-A165-induced endothelial migration in vitro.
- Exon8apab demonstrated efficacy in inhibiting tumor growth and ocular neovascularization in vivo, comparable to non-selective anti-VEGF-A antibodies.
- Elevated VEGF-Axxx levels were observed in patients with proliferative diabetic retinopathy.
Conclusions:
- VEGF-A165-specific antibodies can be therapeutically effective.
- Targeted anti-VEGF-A therapies offer a potentially more effective treatment strategy.
- Further research into isoform-specific antibodies is warranted for ocular neovascularization and cancer treatment.
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