ArticleGynecologic oncology2023
Generation and characterization of humanized affinity-matured EGFL6 antibodies for ovarian cancer therapy.
Article in Gynecologic oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- EGFL6 predicts unfavorable prognosis and serves as a potential indicator in esophageal carcinoma.Discover oncology · 2026Article
- EGFL6 is a novel HER3 ligand, inducing HER3/integrin heterodimers to induce pERK centrosomal deposition and therapeutic resistance.Neoplasia (New York, N.Y.) · 2025Article
- Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116Nature genetics · 2025Article
- Expression and prognostic value of EGF-like domain multiple 6 in uterine corpus endometrial carcinoma and its correlation with immune cell infiltration.Scientific reports · 2025Article
- Egfl6 promotes ovarian cancer progression by enhancing the immunosuppressive functions of tumor-associated myeloid cells.The Journal of clinical investigation · 2024Article
- EGFL6 promotes endometrial cancer cell migration and proliferation.Gynecologic oncology · 2024Article
- Circular RNA vaccine in disease prevention and treatment.Signal transduction and targeted therapy · 2023Review
- Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation.International journal of molecular sciences · 2023Article
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7 authors.
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Abstract
objectivesEpidermal growth factor EGF-like domain multiple-6 (EGFL6) is highly expressed in high grade serous ovarian cancer and promotes both endothelial cell proliferation/angiogenesis and cancer cell proliferation/metastasis. As such it has been implicated as a therapeutic target. As a secreted factor, EGFL6 is a candidate for antibody therapy. The objectives of this study were to create and validate humanized affinity-matured EGFL6 neutralizing antibodies for clinical development.
methodsA selected murine EGFL6 antibody was humanized using CDR grafting to create 26 variant humanized antibodies. These were screened and the lead candidate was affinity matured. Seven humanized affinity-matured EGFL6 antibodies were screened for their ability to block EGFL6 activity on cancer cells in vitro, two of which were selected and tested their therapeutic activity in vivo.
resultsHumanized affinity matured antibodies demonstrated high affinity for EGFL6 (150 pM to 2.67 nM). We found that several humanized affinity-matured EGFL6 antibodies specifically bound to recombinant, and native human EGFL6. Two lead antibodies were able to inhibit EGFL6-mediated (i) cancer cell migration, (ii) proliferation, and (iii) increase in ERK phosphorylation in cancer cells in vitro. Both lead antibodies restricted growth of an EGFL6 expressing ovarian cancer patient derived xenograft. Analysis of treated human tumor xenografts indicated that anti-EGFL6 therapy suppressed angiogenesis, inhibited tumor cell proliferation, and promoted tumor cell apoptosis.
conclusionsOur studies confirm the ability of these humanized affinity-matured antibodies to neutralize EGFL6 and acting as a therapeutic to restrict cancer growth. This work supports the development of these antibody for first-in-human clinical trials.
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