ArticleProceedings of the National Academy of Sciences of the United States of America2016
Targeted vaccination against the bevacizumab binding site on VEGF using 3D-structured peptides elicits efficient antitumor activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02237638 (A Phase I Open-label Clinical Trial, Evaluating the Therapeutic Vaccine hVEGF26-104/RFASE in Patients With Advanced Solid Tumors), which is not on this map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Phase I Open-label Clinical Trial, Evaluating the Therapeutic Vaccine hVEGF26-104/RFASE in Patients With Advanced Solid Tumors
Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Emerging immunologic approaches as cancer anti-angiogenic therapies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Embryonic reprogramming of the tumor vasculature reveals targets for cancer therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anti-angiogenic therapy as potential treatment for adenomyosis.Angiogenesis · 2025Article
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- Vaccine adjuvants for infectious disease in the clinic.Bioengineering & translational medicine · 2024Review
- Mechanisms of Action and Limitations of Monoclonal Antibodies and Single Chain Fragment Variable (scFv) in the Treatment of Cancer.Biomedicines · 2023Review
- Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes.Nature reviews. Clinical oncology · 2021Review
- A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26-104/RFASE in Patients with Advanced Solid Malignancies.The oncologist · 2021Article
- B-cell epitope peptide cancer vaccines: a new paradigm for combination immunotherapies with novel checkpoint peptide vaccine.Future oncology (London, England) · 2020Review
- Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program.BMC immunology · 2020Article
- Antiangiogenic Vascular Endothelial Growth Factor-Blocking Peptides Displayed on the Capsid of an Infectious Oncolytic Parvovirus: Assembly and Immune Interactions.Journal of virology · 2019Article
- Antisense Oligonucleotides Targeting Angiogenic Factors as Potential Cancer Therapeutics.Molecular therapy. Nucleic acids · 2019Review
- Targeting Angiogenesis With Peptide Vaccines.Frontiers in immunology · 2019Review
- Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa.Nature reviews. Clinical oncology · 2018Review
- Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice.Cancer immunology, immunotherapy : CII · 2017Article
- Design, crystal structure and atomic force microscopy study of thioether ligated d,l-cyclic antimicrobial peptides against multidrug resistantChemical science · 2017Article
- The revival of cancer vaccines - The eminent need to activate humoral immunity.Human vaccines & immunotherapeutics · 2017Article
- Reply to Marchiò et al.: Antitumor immune regulation by angiostatic therapy.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- An antivascular vaccine to boost self-immunity and strike the tumor.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Targeting the pro-angiogenic forms of VEGF or inhibiting their expression as anti-cancer strategies.Oncotarget · 2017Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic targeting of the VEGF signaling axis by the VEGF-neutralizing monoclonal antibody bevacizumab has clearly demonstrated clinical benefit in cancer patients. To improve this strategy using a polyclonal approach, we developed a vaccine targeting VEGF using 3D-structured peptides that mimic the bevacizumab binding site. An in-depth study on peptide optimization showed that the antigen's 3D structure is essential to achieve neutralizing antibody responses. Peptide 1 adopts a clear secondary, native-like structure, including the typical cysteine-knot fold, as evidenced by CD spectroscopy. Binding and competition studies with bevacizumab in ELISA and surface plasmon resonance analysis revealed that peptide 1 represents the complete bevacizumab binding site, including the hairpin loop (β5-turn-β6) and the structure-supporting β2-α2-β3 loop. Vaccination with peptide 1 elicited high titers of cross-reactive antibodies to VEGF, with potent neutralizing activity. Moreover, vaccination-induced antisera displayed strong angiostatic and tumor-growth-inhibiting properties in a preclinical mouse model for colorectal carcinoma, whereas antibodies raised with peptides exclusively encompassing the β5-turn-β6 loop (peptides 15 and 20) did not. Immunization with peptide 1 or 7 (murine analog of 1) in combination with the potent adjuvant raffinose fatty acid sulfate ester (RFASE) showed significant inhibition of tumor growth in the B16F10 murine melanoma model. Based on these data, we conclude that this vaccination technology, which is currently being investigated in a phase I clinical trial (NCT02237638), can potentially outperform currently applied anti-VEGF therapeutics.
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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.