Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.
Monoclon Antib Immunodiagn Immunother. 2020 Aug;39(4):135-139. doi: 10.1089/mab.2020.0013. Epub 2020 Jul 9.
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.
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。