Antitumor Activities in Mouse Xenograft Models of Canine Mammary Gland Tumor by Defucosylated Mouse-Dog Chimeric Anti-Epidermal Growth Factor Receptor Antibody (E134Bf)
Antitumor Activities in Mouse Xenograft Models of Canine Mammary Gland Tumor by Defucosylated Mouse-Dog Chimeric Anti-Epidermal Growth Factor Receptor Antibody (E134Bf)
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去岩藻糖基化鼠-狗嵌合抗表皮生长因子受体抗体 (E134Bf) 在小鼠犬乳腺肿瘤异种移植模型中的抗肿瘤活性
DOI：
10.1089/mab.2021.0040
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发表时间：
2022
影响因子：
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通讯作者：
Kato Yukinari
中科院分区：
文献类型：
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作者：
Li Guanjie;Suzuki Hiroyuki;Takei Junko;Asano Teizo;Sano Masato;Tanaka Tomohiro;Harada Hiroyuki;Mizuno Takuya;Ohishi Tomokazu;Kawada Manabu;Kaneko Mika K.;Kato Yukinari
表皮生长因子受体(EGFR)通过基因扩增和/或蛋白过度表达参与肿瘤的恶性转化。在我们之前的研究中，我们研制了一种抗人表皮生长因子受体(HEGFR)的单抗，克隆EMAb-134(小鼠IgG1，kappa)，它能特异性地检测hEGFR和狗的EGFR(DEGFR)。EMAb-134对小鼠IgG2的反义作用在dEGFR过表达的CHO-K1(CHO/dEGFR)细胞中表现出抗体依赖的细胞毒作用(ADCC)和补体依赖的细胞毒作用(CDC)，在CHO/dEGFR细胞的小鼠移植瘤中具有抗肿瘤活性。在本研究中，我们制备了一种脱糖的鼠-狗嵌合抗EGFR单抗(E134Bf)，并用流式细胞仪检测了E134Bf对犬乳腺肿瘤细胞株(SNP)的反应性。此外，E134Bf对SNP细胞有较高的ADCC和CDC活性。E134Bf与犬单核细胞联合应用可显著抑制SNP异种移植瘤的生长。这些结果表明，E134Bf对表达DEGFR的犬乳腺肿瘤具有抗肿瘤作用，可作为抗体治疗方案的一部分。
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 (mAb), clone EMab-134 (mouse IgG1, kappa), which specifically detects both hEGFR and dog EGFR (dEGFR). The defucosylated mouse IgG2aversion of EMab-134 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, we produced a defucosylated mouse-dog chimeric anti-EGFR mAb (E134Bf), and the reactivity of E134Bf against a canine mammary gland tumor cell line (SNP) was examined by flow cytometry. Furthermore, E134Bf highly exerted ADCC and CDC for SNP cells. The administration of E134Bf with canine mononuclear cells significantly suppressed the SNP xenograft growth. These results suggest that E134Bf exerts antitumor effects against dEGFR-expressing canine mammary gland tumors and could be valuable as part of an antibody treatment regimen for them.