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