去岩藻糖基化的鼠-犬嵌合抗 EGFR 抗体在犬肿瘤的小鼠异种移植模型中发挥抗肿瘤活性。

Defucosylated Mouse-Dog Chimeric Anti-EGFR Antibody Exerts Antitumor Activities in Mouse Xenograft Models of Canine Tumors.

机构信息

Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.

Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu-shi 410-0301, Japan.

出版信息

Cells. 2021 Dec 20;10(12):3599. doi: 10.3390/cells10123599.

The epidermal growth factor receptor (EGFR) contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-EGFR monoclonal antibody, namely E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs.

表皮生长因子受体（EGFR）通过基因扩增和蛋白过表达促进肿瘤恶性转化。先前，我们开发了一种抗人 EGFR（hEGFR）的单克隆抗体，即 EMab-134，它具有高灵敏度和特异性地检测 hEGFR 和犬 EGFR（dEGFR）的能力。在本研究中，我们制备了一种去岩藻糖基化的鼠-犬嵌合抗 EGFR 单克隆抗体，即 E134Bf。体外分析表明，E134Bf 对表达内源性 dEGFR 的犬骨肉瘤细胞系（D-17）和犬成纤维细胞系（A-72）具有高度的抗体依赖性细胞毒性和补体依赖性细胞毒性。此外，在小鼠异种移植中，E134Bf 的体内给药显著抑制了 D-17 和 A-72 的发展，与对照犬 IgG 相比。这些结果表明，E134Bf 对表达 dEGFR 的犬科癌症具有抗肿瘤作用，可作为犬抗体治疗方案的一部分具有价值。