Discovery of an Heparin-Binding Epidermal Growth Factor Domain Antibody from a Phage Library and Analysis of Its Inhibitory Effects in SKOV3 Cells.

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cancer Biotherapy and Radiopharmaceuticals Pub Date : 2023-10-01 Epub Date: 2021-09-16 DOI:10.1089/cbr.2021.0123
Peng Lü, Songlin Qiu, Ye Pan, Shenyan Shi, Qian Yu, Feng Yu, Lianjun Miao, Huiying Wang, Keping Chen
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Abstract

Objective: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which binds to the EGF receptor, plays an important role in the occurrence and development of inflammation in various diseases. HB-EGF mediates the progression of ovarian cancer and is associated with disease prognosis. Thus, a specific humanized antibody to HB-EGF with high affinity is important. Methods: In this study, a humanized domain antibody (VH) against HB-EGF was discovered through phage display technology. The domain antibody was expressed in HB2151 cells and purified from the supernatant using protein L, and were used to test the its effect in invasion and migration of ovarian cancer SKOV3. Results: A domain antibody against HB-EGF was discovered, with a dissociation constant of ∼30 nM. Functional assays indicated that the domain antibody inhibited the functions of HB-EGF in promoting invasion and migration of SKOV3 cells. Conclusions: The selected domain antibody is a potential tool for developing novel drugs or therapies to combat ovarian cancer.

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从噬菌体文库中发现一种肝素结合表皮生长因子结构域抗体并分析其对SKOV3细胞的抑制作用。
目的:肝素结合表皮生长因子(EGF)样生长因子(HB-EGF)与EGF受体结合,在各种疾病炎症的发生和发展中起着重要作用。HB-EGF介导卵巢癌症的进展,并与疾病预后相关。因此,具有高亲和力的针对HB-EGF的特异性人源化抗体是重要的。方法:本研究通过噬菌体展示技术发现了一种抗HB-EGF的人源化结构域抗体(VH)。结构域抗体在HB2151细胞中表达,并用蛋白L从上清液中纯化,用于检测其在卵巢癌症SKOV3侵袭和迁移中的作用。结果:发现了一种抗HB-EGF的结构域抗体,其解离常数为~30 nM。功能测定表明,结构域抗体抑制了HB-EGF促进SKOV3细胞侵袭和迁移的功能。结论:所选结构域抗体是开发抗卵巢癌症新药或新疗法的潜在工具。
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来源期刊
CiteScore
7.80
自引率
2.90%
发文量
87
审稿时长
3 months
期刊介绍: Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies. The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.
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