Defucosylated Anti-Epidermal Growth Factor Receptor Monoclonal Antibody (134-mG _2a -f) Exerts Antitumor Activities in Mouse Xenograft Models of Canine Osteosarcoma

<jats:p> 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 IgG <jats:sub>1</jats:sub> , kappa), which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. The mouse IgG <jats:sub>2a</jats:sub> version of EMab-134 (134-mG <jats:sub>2a</jats:sub> ) has antitumor effects toward mouse xenografts of hEGFR-expressing oral squamous cell carcinomas. Furthermore, 134-mG <jats:sub>2a</jats:sub> -f, the defucosylated version of 134-mG <jats:sub>2a</jats:sub> , 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-mG <jats:sub>2a</jats:sub> -f against canine cancer cells with endogenous dEGFR was first examined by flow cytometry and immunocytochemistry. <jats:italic toggle="yes">In vitro</jats:italic> analysis demonstrated that 134-mG <jats:sub>2a</jats:sub> -f highly exerted ADCC and CDC for a canine osteosarcoma cell line, D-17, which expresses endogenous dEGFR. Moreover, <jats:italic toggle="yes">in vivo</jats:italic> administration of 134-mG <jats:sub>2a</jats:sub> -f significantly suppressed the development of D-17 compared with the results in response to control mouse IgG. These results suggest that 134-mG <jats:sub>2a</jats:sub> -f exerts antitumor effects against dEGFR-expressing canine cancers, and could be valuable as part of an antibody treatment regimen for them. </jats:p>