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Updated: Jan 10, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate anti-proliferative effects
Samuel A Blackman1, Ahlam N Qerqez1, Alison G Lee2
1McKetta Department of Chemical Engineering, The University of Texas at Austin, 200 E Dean Keeton St, Austin, TX 78712.
Abstract:
Antibodies blocking the function of vascular endothelial growth factor A (VEGFA) remain a promising therapeutic strategy, especially when combined with check-point inhibitors, but their efficacy is limited by tumor resistance. This can occur via multiple mechanisms, including upregulation of placental growth factor 2 (PlGF-2), an alternative ligand for VEGF receptor 1 (VEGFR1) and neuropilin receptor 1 (NRP1). Activity of both growth factors is mediated by interactions with multiple receptors and extra-cellular matrix components, which complicates efforts to understand their contributions to cancer progression. To complement existing antibodies, we discovered those blocking interactions between PlGF-2 or VEGFA and their shared NRP1 receptor in the presence of heparin. Limiting angiogenesis to promote vascular normalization is one mechanism of anti-VEGF protection; here, anti-VEGFA antibodies blocking interactions with VEGFR1 and NRP1 reduced HUVEC tube formation in a physiological angiogenesis model. By contrast, antibodies binding PlGF-2 or VEGFA to block NRP1 significantly reduced proliferation of Caki-I kidney carcinoma cells in vitro, indicating this receptor mediates additional effects. Interestingly, one antibody exhibited dual-reactive binding to VEGFA and PlGF-2, suggesting a novel therapeutic strategy to prevent PlGF-driven VEGF-resistance. Overall, these antibodies define new mechanisms to disrupt PlGF activity and support a role for NRP1 in cell proliferation.
Insights
New antibodies targeting vascular endothelial growth factor A (VEGFA) and placental growth factor 2 (PlGF-2) interactions with neuropilin receptor 1 (NRP1) show promise in overcoming tumor resistance and inhibiting cancer cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Vascular endothelial growth factor A (VEGFA) inhibitors are promising cancer therapies, but tumor resistance limits efficacy.
- Resistance can arise from upregulation of placental growth factor 2 (PlGF-2), which also binds VEGF receptor 1 (VEGFR1) and neuropilin receptor 1 (NRP1).
- Understanding the complex interactions of VEGFA and PlGF-2 with receptors and extracellular matrix is crucial for developing effective therapies.
Purpose of the Study:
- To develop novel antibodies that block interactions between VEGFA/PlGF-2 and their shared receptor NRP1.
- To investigate the mechanisms by which these antibodies affect angiogenesis and cancer cell proliferation.
- To explore a dual-reactive antibody strategy against both VEGFA and PlGF-2 to overcome resistance.
Main Methods:
- Discovery of antibodies targeting VEGFA/PlGF-2 interactions with NRP1 in the presence of heparin.
- Assessment of anti-VEGFA antibody effects on human umbilical vein endothelial cell (HUVEC) tube formation in an angiogenesis model.
- Evaluation of antibodies blocking PlGF-2 or VEGFA binding to NRP1 on Caki-I kidney carcinoma cell proliferation in vitro.
- Characterization of a dual-reactive antibody binding both VEGFA and PlGF-2.
Main Results:
- Anti-VEGFA antibodies blocking VEGFR1 and NRP1 interactions reduced HUVEC tube formation, suggesting vascular normalization.
- Antibodies blocking VEGFA or PlGF-2 binding to NRP1 significantly inhibited Caki-I kidney carcinoma cell proliferation.
- A novel dual-reactive antibody targeting both VEGFA and PlGF-2 was identified.
- These findings highlight a role for NRP1 in cancer cell proliferation beyond angiogenesis.
Conclusions:
- Novel antibodies targeting VEGFA and PlGF-2 interactions with NRP1 offer new therapeutic strategies.
- Blocking VEGFA/PlGF-2-NRP1 interactions can inhibit tumor cell proliferation and potentially overcome resistance mechanisms.
- A dual-targeting antibody represents a promising approach to combat VEGFA- and PlGF-driven tumor growth.
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