Defucosylated Mouse-Dog Chimeric Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody (H77Bf) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma
Defucosylated Mouse-Dog Chimeric Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody (H77Bf) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma
复制标题
去岩藻糖基化小鼠-狗嵌合抗人表皮生长因子受体 2 单克隆抗体 (H77Bf) 在犬骨肉瘤小鼠异种移植模型中发挥抗肿瘤活性
DOI：
10.1089/mab.2022.0022
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发表时间：
2023
影响因子：
--
通讯作者：
Kato Yukinari
中科院分区：
文献类型：
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作者：
Nanamiya Ren;Ohishi Tomokazu;Suzuki Hiroyuki;Mizuno Takuya;Yoshikawa Takeo;Asano Teizo;Tanaka Tomohiro;Kaneko Mika K.;Kato Yukinari
人表皮生长因子受体2（HER 2）在多种人类癌症类型中已被研究，其过表达和/或基因突变导致预后不良。因此，HER 2是各种癌症类型（包括乳腺癌和胃癌）的重要治疗靶点。我们之前开发了一种抗HER 2单克隆抗体（mAb）H2 Mab-77（小鼠IgG 1，kappa），可高灵敏度和特异性地检测HER 2和犬HER 2（dHER 2）。在这项研究中，我们产生了一个去岩藻糖基化的小鼠-狗嵌合抗HER 2单抗（H77 Bf），并研究了对犬骨肉瘤D-17细胞的反应性。H77 Bf在体外对D-17细胞具有抗体依赖性细胞毒作用和补体依赖性细胞毒作用，在体内也具有较强的抗肿瘤活性。这些结果表明，H77 Bf对表达dHER 2的犬肿瘤发挥抗肿瘤作用，并可能作为其抗体治疗方案的一部分有价值。
Human epidermal growth factor receptor 2 (HER2) has been studied in many human cancer types, and its overexpression and/or gene mutation contribute to the poor prognosis. Therefore, HER2 is an important therapeutic target in various cancer types, including breast and gastric cancers. We previously developed an anti-HER2 monoclonal antibody (mAb), H2Mab-77 (mouse IgG1, kappa), which detects HER2 and dog HER2 (dHER2) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-HER2 mAb (H77Bf), and investigated the reactivity against canine osteosarcoma D-17 cells by flow cytometry. Furthermore, we showed that H77Bf exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against D-17 cellsin vitroand exhibited the potent antitumor activityin vivo. These results suggest that H77Bf exerts antitumor effects against dHER2-expressing canine tumors and could be valuable as part of an antibody treatment regimen for them.