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HMab-19,一种抗人表皮生长因子受体2单克隆抗体,在小鼠口腔癌异种移植模型中发挥抗肿瘤活性。

HMab-19, an anti-human epidermal growth factor receptor 2 monoclonal antibody exerts antitumor activity in mouse oral cancer xenografts.

作者信息

Takei Junko, Kaneko Mika Kato, Ohishi Tomokazu, Kawada Manabu, Harada Hiroyuki, Kato Yukinari

机构信息

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.

出版信息

Exp Ther Med. 2020 Aug;20(2):846-853. doi: 10.3892/etm.2020.8765. Epub 2020 May 18.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c312/7388441/3ee78ccf5b61/etm-20-02-0846-g00.jpg

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