Antitumor Activities in Mouse Xenograft Models of Canine Fibroblastic Tumor by Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody
Antitumor Activities in Mouse Xenograft Models of Canine Fibroblastic Tumor by Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody
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DOI：
10.1089/mab.2021.0059
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发表时间：
2022-04-01
影响因子：
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通讯作者：
Kato, Yukinari
中科院分区：
文献类型：
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作者：
Goto, Nohara;Suzuki, Hiroyuki;Kato, Yukinari
表皮生长因子受体（EGFR）通过基因扩增和/或蛋白质过表达参与肿瘤恶性。先前开发了一种抗人EGFR（hEGFR）单克隆抗体（克隆EMab-134），可明确检测hEGFR和犬EGFR（dEGFR）。EMab-134的去岩藻糖基化小鼠IgG（2a）版本（134-mG（2a）-f）在dEGFR过表达的CHO-K1（CHO/dEGFR）细胞中显示抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC），并在CHO/dEGFR细胞的小鼠异种移植物中显示抗肿瘤活性。在这项研究中，它表明，134-mG（2a）-f与犬成纤维细胞肿瘤细胞系（A-72）使用流式细胞术和免疫细胞化学反应。此外，134-mG（2a）-f对A-72细胞具有ADCC和CDC作用。给予134-mG（2a）-f显著抑制A-72异种移植物生长。这些结果表明，134-mG（2a）-f对表达dEGFR的犬成纤维细胞肿瘤具有抗肿瘤作用。
The epidermal growth factor receptor (EGFR) is involved in tumor malignancy through gene amplification and/or protein overexpression. An anti-human EGFR (hEGFR) monoclonal antibody (clone EMab-134), which explicitly detects hEGFR and dog EGFR (dEGFR), was previously developed. The defucosylated mouse IgG(2a) version of EMab-134 (134-mG(2a)-f) exhibits antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells and antitumor activities in mouse xenografts of CHO/dEGFR cells. In this study, it was shown that 134-mG(2a)-f reacts with a canine fibroblastic tumor cell line (A-72) using flow cytometry and immunocytochemistry. Furthermore, 134-mG(2a)-f exerted ADCC and CDC on A-72 cell line. The administration of 134-mG(2a)-f significantly inhibited the A-72 xenograft growth. These results suggest that 134-mG(2a)-f exerts antitumor effects on dEGFR-expressing canine fibroblastic tumors.