Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody (134-mG2a-f) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma
Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody (134-mG2a-f) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma
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去岩藻糖基化抗表皮生长因子受体单克隆抗体 (134-mG2a-f) 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.2021.0036
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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：
Nanamiya Ren;Takei Junko;Ohishi Tomokazu;Asano Teizo;Tanaka Tomohiro;Sano Masato;Nakamura Takuro;Yanaka Miyuki;Handa Saori;Tateyama Nami;Harigae Yasuhiro;Saito Masaki;Suzuki Hiroyuki;Kawada Manabu;Kaneko Mika K.;Kato Yukinari
表皮生长因子受体(EGFR)是一种跨膜糖蛋白。尽管EGFR在正常细胞中是生理必需的，但它通过基因扩增和/或蛋白过度表达促进肿瘤细胞中的信号级联反应，从而促进肿瘤的恶性发展。我们先前研制了一种抗人表皮生长因子受体(HEGFR)的单抗，EMAb-134(小鼠IgG1，kappa)，它检测hEGFR和狗的EGFR(DEGFR)，具有很高的敏感性和特异性。EMAb-134(134-mG2a)的小鼠IgG2抗体对表达hEGFR的口腔鳞癌小鼠移植瘤具有抗肿瘤作用。此外，134-mG2a-f，即134-mG2a-f，在dEGFR过表达的CHO-K1(CHO/dEGFR)细胞中表现出抗体依赖的细胞毒性(ADCC)和补体依赖的细胞毒性(CDC)，并在CHO/dEGFR细胞的小鼠移植瘤中具有抗肿瘤活性。本文首次用流式细胞术和免疫细胞化学方法检测了134-mG2a-f对犬肿瘤细胞与内源性dEGFR的反应性。体外分析表明，134-mG2a-f对表达内源性dEGFR的犬骨肉瘤细胞株D-17具有较高的ADCC和CDC活性。此外，在体内给药134-mG2a-f与对照小鼠免疫球蛋白相比，显著抑制了D-17的发展。这些结果表明，134-mG2a-f对表达dEGFR的犬癌具有抗肿瘤作用，可作为抗体治疗方案的一部分。
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein. Although EGFR is physiologically essential in normal cells, it contributes to tumor malignancy through gene amplification and/or protein overexpression, which augment signaling cascades in tumor cells. We previously developed an anti-human EGFR (hEGFR) monoclonal antibody (mAb), EMab-134 (mouse IgG1, kappa), which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. The mouse IgG2aversion of EMab-134 (134-mG2a) has antitumor effects toward mouse xenografts of hEGFR-expressing oral squamous cell carcinomas. Furthermore, 134-mG2a-f, the defucosylated version of 134-mG2a, 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. Herein, the reactivity of 134-mG2a-f against canine cancer cells with endogenous dEGFR was first examined by flow cytometry and immunocytochemistry.In vitroanalysis demonstrated that 134-mG2a-f highly exerted ADCC and CDC for a canine osteosarcoma cell line, D-17, which expresses endogenous dEGFR. Moreover,in vivoadministration of 134-mG2a-f significantly suppressed the development of D-17 compared with the results in response to control mouse IgG. These results suggest that 134-mG2a-f exerts antitumor effects against dEGFR-expressing canine cancers, and could be valuable as part of an antibody treatment regimen for them.