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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。

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

机构信息

School of Life Sciences, Jiangsu University, Zhenjiang, China.

General Biological System, Inc., Chuzhou, China.

出版信息

Cancer Biother Radiopharm. 2023 Oct;38(8):572-579. doi: 10.1089/cbr.2021.0123. Epub 2021 Sep 16.

DOI:10.1089/cbr.2021.0123
PMID:34529926
Abstract

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. 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. 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. The selected domain antibody is a potential tool for developing novel drugs or therapies to combat ovarian cancer.

摘要

肝素结合表皮生长因子(EGF)样生长因子(HB-EGF)与表皮生长因子受体结合,在各种疾病的炎症发生和发展中发挥重要作用。HB-EGF 介导卵巢癌的进展,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非常重要。在这项研究中,通过噬菌体展示技术发现了针对 HB-EGF 的人源化结构域抗体(VH)。该结构域抗体在 HB2151 细胞中表达,并使用蛋白 L 从上清液中纯化出来,并用于测试其在卵巢癌 SKOV3 侵袭和迁移中的作用。发现了一种针对 HB-EGF 的结构域抗体,其解离常数约为 30 nM。功能分析表明,该结构域抗体抑制了 HB-EGF 促进 SKOV3 细胞侵袭和迁移的功能。所选的结构域抗体是开发用于对抗卵巢癌的新型药物或疗法的潜在工具。

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