ArticlePloS one2018
Generation of high-affinity, internalizing anti-FGFR2 single-chain variable antibody fragment fused with Fc for targeting gastrointestinal cancers.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Advancements in research leveraging phage display technology for gastric cancer diagnosis and treatment.Frontiers in microbiology · 2025Review
- The Potential of Single-Chain Variable Fragment Antibody: Role in Future Therapeutic and Diagnostic Biologics.Journal of immunology research · 2024Review
- Chemical Conjugation in Drug Delivery Systems.Frontiers in chemistry · 2022Review
- Review
- Modular self-assembly system for development of oligomeric, highly internalizing and potent cytotoxic conjugates targeting fibroblast growth factor receptors.Journal of biomedical science · 2021Article
- Development and Characterization of a Novel Peptide-Drug Conjugate with DM1 for Treatment of FGFR2-Positive Tumors.Biomedicines · 2021Article
- 2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.Journal of oncology · 2021Review
- Discovery and Validation of Serum Autoantibodies Against Tumor-Associated Antigens as Biomarkers in Gastric Adenocarcinoma Based on the Focused Protein Arrays.Clinical and translational gastroenterology · 2020Observational
- Tackling solid tumour therapy with small-format drug conjugates.Antibody therapeutics · 2020Review
- FGF2-Derived PeptibodyF2-MMAE Conjugate for Targeted Delivery of Cytotoxic Drugs into Cancer Cells Overexpressing FGFR1.Cancers · 2020Article
- FGFR1 clustering with engineered tetravalent antibody improves the efficiency and modifies the mechanism of receptor internalization.Molecular oncology · 2020Article
- Site-Specific, Stoichiometric-Controlled, PEGylated Conjugates of Fibroblast Growth Factor 2 (FGF2) with Hydrophilic Auristatin Y for Highly Selective Killing of Cancer Cells Overproducing Fibroblast Growth Factor Receptor 1 (FGFR1).Molecular pharmaceutics · 2020Article
- Novel monoclonal antibodies against thymidine kinase 1 and their potential use for the immunotargeting of lung, breast and colon cancer cells.Cancer cell international · 2020Article
- Fibroblast growth factor receptors as treatment targets in clinical oncology.Nature reviews. Clinical oncology · 2019Review
- Targeting Cellular Trafficking of Fibroblast Growth Factor Receptors as a Strategy for Selective Cancer Treatment.Journal of clinical medicine · 2018Review
- High Affinity Promotes Internalization of Engineered Antibodies Targeting FGFR1.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2). The binders were selected from the human single chain variable fragment scFv phage display libraries Tomlinson I + J and showed high specificity and binding affinity towards human FGFR2 with nanomolar KD values. To improve the affinity of the best binder selected, scFvF7, we reformatted it to a bivalent diabody format, or fused it with the Fc region (scFvF7-Fc). The scFvF7-Fc antibody construct presented the highest affinity for FGFR2, with a KD of 0.76 nM, and was selectively internalized into cancer cells overexpressing FGFR2, Snu-16 and NCI-H716. Finally, we prepared a conjugate of scFvF7-Fc with the cytotoxic drug monomethyl-auristatin E (MMAE) and evaluated its cytotoxicity. The conjugate delivered MMAE selectively to FGFR2-positive tumor cells. These results indicate that scFvF7-Fc-vcMMAE is a highly potent molecule for the treatment of cancers with FGFR2 overexpression.
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