Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer
Development of an Anti-HER2 Monoclonal Antibody H2Mab-139 Against Colon Cancer
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DOI：
10.1089/mab.2017.0052
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发表时间：
2018-02-01
影响因子：
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通讯作者：
Kato, Yukinari
中科院分区：
文献类型：
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作者：
Kaneko, Mika K.;Yamada, Shinji;Kato, Yukinari
已经报道了人表皮生长因子受体2（HER 2）在几种癌症中的表达，例如乳腺癌、胃癌、肺癌、胰腺癌和结肠直肠癌。HER 2在这些癌症中过表达，并与不良临床结局相关。曲妥珠单抗是一种人源化抗HER 2抗体，可为HER 2过表达乳腺癌和胃癌患者提供显著的生存获益。在本研究中，我们开发了一种新的抗HER 2单克隆抗体（mAb），H（2）Mab-139（IgG（1），kappa），并使用流式细胞术、western blot和免疫组织化学分析来研究其对结肠癌的作用。流式细胞术分析显示，H（2）Mab-139与结肠癌细胞系如Caco-2、HCT-116、HCT-15、HT-29、LS 174 T、COLO 201、科洛205、HCT-8、SW 1116和DLD-1反应。虽然H（2）Mab-139在蛋白质印迹上与LN 229/HER 2细胞强烈反应，但我们在结肠癌细胞系中未观察到HER 2的特异性信号。免疫组织化学分析显示H（2）Mab-139对结肠癌的敏感性和特异性反应，表明H（2）Mab-139可用于使用流式细胞术和免疫组织化学分析检测结肠癌中HER 2过表达。
Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H(2)Mab-139 (IgG(1), kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses. Flow cytometry analysis revealed that H(2)Mab-139 reacted with colon cancer cell lines, such as Caco-2, HCT-116, HCT-15, HT-29, LS 174T, COLO 201, COLO 205, HCT-8, SW1116, and DLD-1. Although H(2)Mab-139 strongly reacted with LN229/HER2 cells on the western blot, we did not observe a specific signal for HER2 in colon cancer cell lines. Immunohistochemical analyses revealed sensitive and specific reactions of H(2)Mab-139 against colon cancers, indicating that H(2)Mab-139 is useful in detecting HER2 overexpression in colon cancers using flow cytometry and immunohistochemical analyses.