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去岩藻糖基化抗表皮生长因子受体单克隆抗体在犬成纤维细胞瘤小鼠异种移植模型中的抗肿瘤活性

Antitumor Activities in Mouse Xenograft Models of Canine Fibroblastic Tumor by Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody.

作者信息

Goto Nohara, Suzuki Hiroyuki, Ohishi Tomokazu, Harakawa Akiko, Li Guanjie, Saito Masaki, Takei Junko, Tanaka Tomohiro, Asano Teizo, Sano Masato, Kawada Manabu, Kaneko Mika K, Kato Yukinari

机构信息

Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Numazu-shi, Shizuoka, Japan.

出版信息

Monoclon Antib Immunodiagn Immunother. 2022 Apr;41(2):67-73. doi: 10.1089/mab.2021.0059. Epub 2022 Apr 4.

Abstract

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 version of EMab-134 (134-mG-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-f reacts with a canine fibroblastic tumor cell line (A-72) using flow cytometry and immunocytochemistry. Furthermore, 134-mG-f exerted ADCC and CDC on A-72 cell line. The administration of 134-mG-f significantly inhibited the A-72 xenograft growth. These results suggest that 134-mG-f exerts antitumor effects on dEGFR-expressing canine fibroblastic tumors.

摘要

表皮生长因子受体(EGFR)通过基因扩增和/或蛋白过表达参与肿瘤的恶性发展。先前已开发出一种抗人EGFR(hEGFR)单克隆抗体(克隆号EMab - 134),该抗体可特异性检测hEGFR和犬EGFR(dEGFR)。去岩藻糖基化的小鼠IgG形式的EMab - 134(134 - mG - f)在dEGFR过表达的CHO - K1(CHO/dEGFR)细胞中表现出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模型中具有抗肿瘤活性。在本研究中,通过流式细胞术和免疫细胞化学表明134 - mG - f与犬成纤维细胞瘤细胞系(A - 72)发生反应。此外,134 - mG - f对A - 72细胞系发挥了ADCC和CDC作用。给予134 - mG - f可显著抑制A - 72异种移植瘤的生长。这些结果表明134 - mG - f对表达dEGFR的犬成纤维细胞瘤具有抗肿瘤作用。

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