ArticleAngiogenesis2016
Aflibercept exhibits VEGF binding stoichiometry distinct from bevacizumab and does not support formation of immune-like complexes.
Article in Angiogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- A Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients With Metastatic Renal Cell Carcinoma (ECOG-ACRIN [E4805]).Clinical genitourinary cancer · 2017Trial
- Molecular Determinants of Intravitreal Anti-VEGF Durability: Drug Architecture, Intraocular Pharmacokinetics, Target Biology and Treatment Resistance.International journal of molecular sciences · 2026Review
- Pharmacological principles of intravitreal drug therapy and their implications for clinical practice: a primer for the ophthalmologist.Eye (London, England) · 2026Review
- IMM2510, a novel anti-PD-L1/VEGF bispecific antibody for cancer immunotherapy.Antibody therapeutics · 2026Article
- Article
- Comparative Pharmacokinetic Analysis of Aflibercept and Brolucizumab in Human Aqueous Humor Using Nano-Surface and Molecular-Orientation Limited Proteolysis.International journal of molecular sciences · 2025Article
- Nonclinical Similarity of the Biosimilar Candidate ABP 938 with Aflibercept Reference Product.Ophthalmology and therapy · 2025Article
- Characterization of Receptor Binding Affinity for Vascular Endothelial Growth Factor with Interferometric Imaging Sensor.Biosensors · 2024Article
- Efficient Expression of Functionally Active Aflibercept with Designed N-glycans.Antibodies (Basel, Switzerland) · 2024Article
- Sustained and Efficient Delivery of Antivascular Endothelial Growth Factor by the Adeno-associated Virus for the Treatment of Corneal Neovascularization: An Outlook for Its Clinical Translation.Journal of ophthalmology · 2024Review
- Comparison of Bevacizumab and Aflibercept for Suppression of Angiogenesis in Human Retinal Microvascular Endothelial Cells.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life.Communications biology · 2022Article
- Effect of bevacizumab combined with chemotherapy on SDF-1 and CXCR4 in epithelial ovarian cancer and its prognosis.World journal of surgical oncology · 2022Article
- Efficacy and Safety of Anti-Vascular Endothelial Growth Factor Monotherapies for Neovascular Age-Related Macular Degeneration: A Mixed Treatment Comparison.Frontiers in pharmacology · 2021Article
- Tumor necrosis factor α inhibition overcomes immunosuppressive M2b macrophage-induced bevacizumab resistance in triple-negative breast cancer.Cell death & disease · 2020Article
- Structure-Guided Molecular Engineering of a Vascular Endothelial Growth Factor Antagonist to Treat Retinal Diseases.Cellular and molecular bioengineering · 2020Article
- Aflibercept ameliorates retinal pericyte loss and restores perfusion in streptozotocin-induced diabetic mice.BMJ open diabetes research & care · 2020Article
- Heparin potentiates Avastin-mediated inhibition of VEGF binding to fibronectin and rescues Avastin activity at acidic pH.The Journal of biological chemistry · 2019Article
- Review
- Co-inhibition of PGF and VEGF blocks their expression in mononuclear phagocytes and limits neovascularization and leakage in the murine retina.Journal of neuroinflammation · 2019Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials. However, questions persist regarding its safety, as bevacizumab can form large complexes with dimeric VEGF165, resulting in multimerization of the Fc domain and platelet activation. Here, we compare binding stoichiometry, Fcγ receptor affinity, platelet activation, and binding to epithelial and endothelial cells in vitro for bevacizumab and aflibercept, in the absence or presence of VEGF. In contrast to bevacizumab, aflibercept forms a homogenous 1:1 complex with each VEGF dimer. Unlike multimeric bevacizumab:VEGF complexes, the monomeric aflibercept:VEGF complex does not exhibit increased affinity for low-affinity Fcγ receptors, does not activate platelets, nor does it bind to the surface of epithelial or endothelial cells to a greater degree than unbound aflibercept or control Fc. The latter finding reflects the fact that aflibercept binds VEGF in a unique manner, distinct from antibodies not only blocking the amino acids necessary for VEGFR1/R2 binding but also occluding the heparin-binding site on VEGF165.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.