ArticleSignal transduction and targeted therapy
Human IgG1 antibodies suppress angiogenesis in a target-independent manner.
Article in Signal transduction and targeted therapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
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- Regulatable Complement Inhibition of the Alternative Pathway Mitigates Wet Age-Related Macular Degeneration Pathology in a Mouse Model.Translational vision science & technology · 2023Article
- Antibody therapeutics for epithelial ovarian cancer.Expert opinion on biological therapy · 2022Article
- Protein and polypeptide mediated delivery to the eye.Advanced drug delivery reviews · 2022Review
- Engineered DNA-encoded monoclonal antibodies targeting Plasmodium falciparum circumsporozoite protein confer single dose protection in a murine malaria challenge model.Scientific reports · 2022Article
- A Charge Variant of Bevacizumab Offers Enhanced FcRn-Dependent Pharmacokinetic Half-Life and Efficacy.Pharmaceutical research · 2022Article
- Loss of Id3 (Inhibitor of Differentiation 3) Increases the Number of IgM-Producing B-1b Cells in Ischemic Skeletal Muscle Impairing Blood Flow Recovery During Hindlimb Ischemia.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Systematic Analysis of the Expression and Prognosis of Fcγ Receptors in Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2022Article
- Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cellular Fitness Phenotypes of Cancer Target Genes from Oncobiology to Cancer Therapeutics.Cells · 2021Article
- Integrative Bioinformatics Approaches to Screen Potential Prognostic Immune-Related Genes and Drugs in the Cervical Cancer Microenvironment.Frontiers in genetics · 2020Article
- The Design, Characterizations, and Tumor Angiogenesis Inhibition of a Multi-Epitope Peptibody With bFGF/VEGFA.Frontiers in oncology · 2020Article
- Exploring the Immunological Mechanisms Underlying the Anti-vascular Endothelial Growth Factor Activity in Tumors.Frontiers in immunology · 2019Review
- The role of Wnt signaling pathway in atherosclerosis and its relationship with angiogenesis.Experimental and therapeutic medicine · 2018Article
- New Therapies of Neovascular AMD-Beyond Anti-VEGFs.Vision (Basel, Switzerland) · 2018Review
- Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector cells.Scientific reports · 2017Article
- Molecular Checkpoint Decisions Made by Subverted Vascular Niche Transform Indolent Tumor Cells into Chemoresistant Cancer Stem Cells.Cancer cell · 2017Article
- HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1PJCI insight · 2016Article
- Intravenous immune globulin suppresses angiogenesis in mice and humans.Signal transduction and targeted therapyArticle
Corrections and comments
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Authors and funding
36 authors at 13 institutions in 7 countries.
Funding
Abstract
Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world's population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type and FcγR humanized mice. This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown, Fc cleavage, IgG-Fc inhibition, disruption of Fc-FcγR interaction, or elimination of FcRγ-initated signaling. Furthermore, bevacizumab's Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice. Finally, mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis. These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.
Identifiers
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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.