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

Nohara Goto, Hiroyuki Suzuki, T. Ohishi, Akiko Harakawa, Guanjie Li, Masaki Saito, Junko Takei, Tomohiro Tanaka, Teizo Asano, M. Sano, M. Kawada, M. Kaneko, Y. Kato
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引用次数: 5

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 IgG2a version of EMab-134 (134-mG2a-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-mG2a-f reacts with a canine fibroblastic tumor cell line (A-72) using flow cytometry and immunocytochemistry. Furthermore, 134-mG2a-f exerted ADCC and CDC on A-72 cell line. The administration of 134-mG2a-f significantly inhibited the A-72 xenograft growth. These results suggest that 134-mG2a-f exerts antitumor effects on dEGFR-expressing canine fibroblastic tumors.
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去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。
表皮生长因子受体(EGFR)通过基因扩增和/或蛋白过表达参与恶性肿瘤的发生。一种抗人EGFR (hEGFR)单克隆抗体(克隆EMab-134),可明确检测hEGFR和狗EGFR (dEGFR)。去聚焦的小鼠IgG2a版本的EMab-134 (134-mG2a-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物中表现出抗肿瘤活性。本研究通过流式细胞术和免疫细胞化学方法发现134-mG2a-f与犬成纤维肿瘤细胞系(a- 72)发生反应。此外,134-mG2a-f对A-72细胞株具有ADCC和CDC作用。134-mG2a-f显著抑制了A-72异种移植物的生长。提示134-mG2a-f对表达degfr的犬成纤维细胞肿瘤具有抗肿瘤作用。
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49
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