Takei Junko, Kaneko Mika Kato, Ohishi Tomokazu, Kawada Manabu, Harada Hiroyuki, Kato Yukinari
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Exp Ther Med. 2020 Aug;20(2):846-853. doi: 10.3892/etm.2020.8765. Epub 2020 May 18.
Human epidermal growth factor receptor 2 (HER2) is reported to be overexpressed in breast cancers and is associated with poor clinical outcome. Trastuzumab is a humanized anti-HER2 antibody that offers significant survival benefits to patients with HER2-overexpressing breast cancer. In this study, a novel anti-HER2 monoclonal antibody (mAb), HMab-19 (IgG, kappa) was developed. Antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antitumor activity of HMab-19 were investigated using both breast cancer and oral cancer cell lines. HMab-19 demonstrated cytotoxicity in BT-474 (a human breast cancer cell line) and HSC-2 or SAS (human oral cancer cell lines). HMab-19 also possessed both ADCC and CDC activity against BT-474, HSC-2, and SAS cell lines. In comparison to control mouse IgG, HMab-19 significantly reduced tumor development in BT-474, HSC-2, and SAS xenografts. Collectively, these results suggest that treatment with HMab-19 may be a useful therapy for patients with HER2-expressing breast and oral cancers.
据报道,人表皮生长因子受体2(HER2)在乳腺癌中过表达,且与不良临床预后相关。曲妥珠单抗是一种人源化抗HER2抗体,可为HER2过表达的乳腺癌患者带来显著的生存益处。在本研究中,研发了一种新型抗HER2单克隆抗体(mAb)HMab-19(IgG,κ)。使用乳腺癌和口腔癌细胞系研究了HMab-19的抗体依赖性细胞毒性(ADCC)、补体依赖性细胞毒性(CDC)和抗肿瘤活性。HMab-19在BT-474(一种人乳腺癌细胞系)以及HSC-2或SAS(人口腔癌细胞系)中表现出细胞毒性。HMab-19对BT-474、HSC-2和SAS细胞系也具有ADCC和CDC活性。与对照小鼠IgG相比,HMab-19显著减少了BT-474、HSC-2和SAS异种移植瘤的生长。总体而言,这些结果表明,HMab-19治疗可能是HER2表达型乳腺癌和口腔癌患者的一种有效治疗方法。