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Updated: Sep 30, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy
1Department of Molecular and Cell Biology, ImClone Systems Incorporated, New York, USA. larryw@imclone.com
Abstract:
Biological evidence suggests that interference with the function of the angiogenic growth factor receptor VEGFR2 (flk1/KDR) is a particularly promising strategy to inhibit tumor-induced angiogenesis. Proof of concept was established by developing a monoclonal rat anti-mouse VEGFR2 antibody (DC101) and showing that it potently blocked the binding of VEGF to its receptor, inhibited VEGF-induced signaling, and strongly blocked tumor growth in mice through an anti-angiogenic mechanism. Since DC101 does not cross-react with the human VEGFR2 KDR, anti-KDR monoclonal antibodies were generated by standard hybridoma technology and by using phage display library. High affinity antibodies (Kd = 4.9 x 10(-10)-1.1 x 10(-9) M) were found with both approaches. The anti-KDR antibodies compete on an equimolar basis with VEGF for binding to KDR and inhibit with similar potency the VEGF-induced signaling and mitogenesis in human endothelial cells. Although these antibodies cannot be tested for in vivo efficacy in standard murine tumor models because of lack of species cross-reactivity, the similarity of their in vitro properties with those of DC101 suggests that they may be effective in blocking KDR function in vivo.
Insights
Targeting the vascular endothelial growth factor receptor 2 (VEGFR2) inhibits tumor growth. New monoclonal antibodies targeting human VEGFR2 show high affinity and block tumor angiogenesis, suggesting potential therapeutic applications.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor-induced angiogenesis is crucial for cancer growth.
- Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) is a key target for anti-angiogenic therapy.
- A mouse anti-VEGFR2 antibody (DC101) demonstrated efficacy in blocking tumor growth.
Purpose of the Study:
- To develop high-affinity monoclonal antibodies targeting human VEGFR2 (KDR).
- To evaluate the in vitro efficacy of these antibodies in blocking VEGF binding and signaling.
- To assess the potential of these antibodies for anti-angiogenic cancer therapy.
Main Methods:
- Generation of monoclonal antibodies against human VEGFR2 using hybridoma technology and phage display.
- Measurement of antibody affinity using surface plasmon resonance.
- Assessment of antibody function through in vitro assays measuring VEGF binding, signaling inhibition, and endothelial cell proliferation.
Main Results:
- High-affinity monoclonal antibodies (Kd = 4.9 x 10(-10)-1.1 x 10(-9) M) targeting human VEGFR2 were successfully generated.
- These antibodies effectively competed with VEGF for KDR binding.
- The antibodies potently inhibited VEGF-induced signaling and mitogenesis in human endothelial cells.
Conclusions:
- Monoclonal antibodies targeting human VEGFR2 exhibit high affinity and potent in vitro anti-angiogenic activity.
- These antibodies show promise as a therapeutic strategy for inhibiting tumor-induced angiogenesis.
- Further in vivo studies are warranted to confirm efficacy in human cancer models.
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