Kato Yukinari, Ohishi Tomokazu, Yamada Shinji, Itai Shunsuke, Takei Junko, Sano Masato, Nakamura Takuro, Harada Hiroyuki, Kawada Manabu, Kaneko Mika K
1Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
2New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.
Monoclon Antib Immunodiagn Immunother. 2019 Aug;38(4):157-161. doi: 10.1089/mab.2019.0017. Epub 2019 Jun 14.
The expression of human epidermal growth factor receptor 2 (HER2) has been reported to be overexpressed in several cancers, such as breast, lung, gastric, pancreatic, and colorectal cancers, and be 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), HMab-41 (IgG, kappa), and the antitumor activity of HMab-41 was investigated using mouse xenograft models. Caco-2 cells (human colon cancer cell line), which expresses HER2, were subcutaneously implanted into the flanks of nude mice. HMab-41 and control mouse IgG were injected three times into the peritoneal cavity of mice. HMab-41 significantly reduced tumor development of Caco-2 xenograft in comparison with the control mouse IgG on days 5, 8, 11, 15, and 19. Taken together, these results suggest that HMab-41 is useful for antibody therapy against HER2-expressing colon cancers.
据报道，人类表皮生长因子受体2（HER2）在多种癌症中过表达，如乳腺癌、肺癌、胃癌、胰腺癌和结直肠癌，且与不良临床预后相关。曲妥珠单抗，一种人源化抗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。在本研究中，我们开发了一种新型抗HER2单克隆抗体（mAb），HMab-41（IgG，κ），并使用小鼠异种移植模型研究了HMab-41的抗肿瘤活性。将表达HER2的Caco-2细胞（人结肠癌细胞系）皮下植入裸鼠侧腹。将HMab-41和对照小鼠IgG经腹腔注射到小鼠体内3次。与对照小鼠IgG相比，在第5、8、11、15和19天，HMab-41显著抑制了Caco-2异种移植瘤的生长。综上所述，这些结果表明HMab-41可用于针对表达HER2的结肠癌的抗体治疗。
