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

Q3 Medicine Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Pub Date : 2022-06-06 DOI:10.1089/mab.2022.0009

Tomohiro Tanaka, T. Ohishi, Masaki Saito, Hiroyuki Suzuki, M. Kaneko, M. Kawada, Y. Kato

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引用次数: 4

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 IgG1, kappa), which specifically detects both hEGFR and dog EGFR (dEGFR). 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 Chinese hamster ovary-K1 (CHO/dEGFR) cells and antitumor activities in mouse xenografts of CHO/dEGFR cells. In this study, the reactivity of 134-mG2a-f against a canine mammary gland tumor cell line (SNP) was examined by flow cytometry and immunocytochemistry. Furthermore, 134-mG2a-f highly exerted ADCC and CDC for SNP. The administration of 134-mG2a-f significantly suppressed the SNP xenograft growth. These results suggest that 134-mG2a-f exerts antitumor effects against dEGFR-expressing canine mammary gland tumors, and could be valuable as part of an antibody treatment regimen for them.

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去聚焦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瘤模型中显示抗肿瘤活性。

表皮生长因子受体(EGFR)通过基因扩增和/或蛋白过表达参与肿瘤恶性。在我们之前的研究中，我们开发了一种抗人EGFR (hEGFR)单克隆抗体，克隆EMab-134(小鼠IgG1, kappa)，可以特异性检测hEGFR和狗EGFR (dEGFR)。去聚焦小鼠IgG2a版本的EMab-134 (134-mG2a-f)在dEGFR过表达的中国鼠卵巢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)，并在CHO/dEGFR细胞的小鼠异种移植物中表现出抗肿瘤活性。本研究采用流式细胞术和免疫细胞化学检测了134-mG2a-f对犬乳腺肿瘤细胞系(SNP)的反应性。此外，134-mG2a-f高度发挥ADCC和CDC对SNP的作用。134-mG2a-f显著抑制了SNP异种移植物的生长。这些结果表明，134-mG2a-f对表达degfr的犬乳腺肿瘤具有抗肿瘤作用，可以作为抗体治疗方案的一部分。

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Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Medicine-Immunology and Allergy

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4.80

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