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