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Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody (134-mG 2a -f) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma

2022; Mary Ann Liebert, Inc.; Volume: 41; Issue: 1 Linguagem: Inglês

10.1089/mab.2021.0036

2167-9436

Ren Nanamiya, Junko Takei, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Masato Sano, Takuro Nakamura, Miyuki Yanaka, Saori Handa, Nami Tateyama, Yasuhiro Harigae, Masaki Saito, Hiroyuki Suzuki, Manabu Kawada, Mika K. Kaneko, Yukinari Kato,

Glycosylation and Glycoproteins Research

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 IgG2a version 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 vitro analysis demonstrated that 134-mG2a-f highly exerted ADCC and CDC for a canine osteosarcoma cell line, D-17, which expresses endogenous dEGFR. Moreover, in vivo administration 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.