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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乳腺肿瘤小鼠异种移植模型中发挥抗肿瘤活性。

Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Exerted Antitumor Activities in Mouse Xenograft Models of Canine Mammary Gland Tumor.

机构信息

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.

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

出版信息

Monoclon Antib Immunodiagn Immunother. 2022 Jun;41(3):142-149. doi: 10.1089/mab.2022.0009. Epub 2022 Jun 6.

Abstract

The epidermal growth factor receptor (EGFR) contributes to tumor malignancy through gene amplification and/or protein overexpression. In our previous study, we developed an anti-human EGFR (hEGFR) monoclonal antibody, clone EMab-134 (mouse IgG, kappa), which specifically detects both hEGFR and dog EGFR (dEGFR). 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 Chinese hamster ovary-K1 (CHO/dEGFR) cells and antitumor activities in mouse xenografts of CHO/dEGFR cells. In this study, the reactivity of 134-mG-f against a canine mammary gland tumor cell line (SNP) was examined by flow cytometry and immunocytochemistry. Furthermore, 134-mG-f highly exerted ADCC and CDC for SNP. The administration of 134-mG-f significantly suppressed the SNP xenograft growth. These results suggest that 134-mG-f exerts antitumor effects against dEGFR-expressing canine mammary gland tumors, and could be valuable as part of an antibody treatment regimen for them.

摘要

表皮生长因子受体(EGFR)通过基因扩增和/或蛋白过表达促进肿瘤恶性程度。在我们之前的研究中,我们开发了一种抗人 EGFR(hEGFR)的单克隆抗体,克隆 EMab-134(鼠 IgG,kappa),它可以特异性地检测 hEGFR 和犬 EGFR(dEGFR)。EMab-134 的去岩藻糖基化鼠 IgG 版本(134-mG-f)在过表达 dEGFR 的中国仓鼠卵巢-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),以及在 CHO/dEGFR 细胞的小鼠异种移植中具有抗肿瘤活性。在这项研究中,通过流式细胞术和免疫细胞化学检查了 134-mG-f 对犬乳腺肿瘤细胞系(SNP)的反应性。此外,134-mG-f 对 SNP 表现出高 ADCC 和 CDC 活性。134-mG-f 的给药显著抑制了 SNP 异种移植物的生长。这些结果表明,134-mG-f 对表达 dEGFR 的犬乳腺肿瘤具有抗肿瘤作用,可作为犬乳腺肿瘤抗体治疗方案的一部分。

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