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HMab-19 抗人表皮生长因子受体 2 单克隆抗体治疗在胰腺癌异种移植模型中发挥抗肿瘤活性。

HMab-19 Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody Therapy Exerts Antitumor Activity in Pancreatic Cancer Xenograft Models.

机构信息

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.

New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.

出版信息

Monoclon Antib Immunodiagn Immunother. 2020 Jun;39(3):61-65. doi: 10.1089/mab.2020.0011. Epub 2020 May 18.

DOI:10.1089/mab.2020.0011
PMID:32423281
Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in breast cancer, gastric, lung, colorectal, oral, and pancreatic cancers. HER2 expression is associated with poor clinical outcomes. An anti-HER2 humanized antibody, trastuzumab, has improved survival rates in patients with HER2-overexpressing breast and gastric cancers. Previously, we established a novel anti-HER2 monoclonal antibody (mAb), HMab-19 (IgG, kappa). It has also been characterized for breast, oral, and colon cancers. In this study, we investigated the antitumor activities of HMab-19 in pancreatic cancer xenograft models. We selected MIA PaCa-2, a pancreatic cancer cell line which expresses HER2. HMab-19 showed high binding affinity (: 1.2 × 10 M) against MIA PaCa-2 cells. Furthermore, HMab-19 significantly reduced tumor development in a MIA PaCa-2 xenograft model. These results suggest that treatment with HMab-19 may be a useful therapy for patients with HER2-expressing pancreatic cancers.

摘要

人表皮生长因子受体 2(HER2)的过表达已在乳腺癌、胃癌、肺癌、结直肠癌、口腔癌和胰腺癌中报道。HER2 表达与不良临床结局相关。抗 HER2 人源化抗体曲妥珠单抗已提高了 HER2 过表达的乳腺癌和胃癌患者的生存率。此前,我们建立了一种新型抗 HER2 单克隆抗体(mAb),HMab-19(IgG,kappa)。它也已被用于乳腺癌、口腔癌和结肠癌的研究。在这项研究中,我们研究了 HMab-19 在胰腺癌异种移植模型中的抗肿瘤活性。我们选择了表达 HER2 的胰腺癌细胞系 MIA PaCa-2。HMab-19 对 MIA PaCa-2 细胞表现出高结合亲和力(Kd:1.2×10-9 M)。此外,HMab-19 显著抑制了 MIA PaCa-2 异种移植模型中的肿瘤发展。这些结果表明,用 HMab-19 治疗可能是治疗 HER2 表达型胰腺癌患者的一种有效方法。

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