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一种抗人表皮生长因子受体 2 单克隆抗体(HMab-19)在胶质母细胞瘤异种移植模型中发挥抗肿瘤活性。

An Antihuman Epidermal Growth Factor Receptor 2 Monoclonal Antibody (HMab-19) Exerts Antitumor Activity in Glioblastoma 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 Aug;39(4):135-139. doi: 10.1089/mab.2020.0013. Epub 2020 Jul 9.

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in glioblastoma as well as breast, gastric, lung, colorectal, and pancreatic cancers. Its expression is associated with poor clinical outcomes. Anti-HER2 antibodies have provided significant survival benefits to patients with HER2-overexpressing breast and gastric cancers. We recently developed an anti-HER2 monoclonal antibody (mAb), HMab-19 (IgG, kappa), by immunizing mice with the extracellular domain of HER2, which is expressed in LN229 glioblastoma cells. In this study, we investigated the antitumor activity of HMab-19 in an LN229 glioblastoma xenograft model. HMab-19 showed high binding affinity (: 1.1 × 10 M) against LN229 cells. Furthermore, HMab-19 significantly reduced tumor development in an LN229 xenograft. These results suggest that treatment with HMab-19 may be a useful therapy for patients with HER2-expressing glioblastomas.

摘要

人表皮生长因子受体 2(HER2)的过表达已在胶质母细胞瘤以及乳腺癌、胃癌、肺癌、结直肠癌和胰腺癌中被报道。其表达与不良的临床结局相关。抗 HER2 抗体为 HER2 过表达的乳腺癌和胃癌患者提供了显著的生存获益。我们最近通过用 HER2 的细胞外结构域免疫小鼠,开发了一种抗 HER2 的单克隆抗体(mAb)HMab-19(IgG,kappa),该抗体在 LN229 胶质母细胞瘤细胞中表达。在这项研究中,我们研究了 HMab-19 在 LN229 胶质母细胞瘤异种移植模型中的抗肿瘤活性。HMab-19 对 LN229 细胞表现出高结合亲和力(Kd=1.1×10-9 M)。此外,HMab-19 显著减少了 LN229 异种移植瘤的发展。这些结果表明,用 HMab-19 治疗可能是治疗 HER2 表达型胶质母细胞瘤患者的一种有效方法。

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