Antitumor Activities in Mouse Xenograft Models of Canine Mammary Gland Tumor by Defucosylated Mouse-Dog Chimeric Anti-Epidermal Growth Factor Receptor Antibody (E134Bf)

Guanjie Li, Hiroyuki Suzuki, Junko Takei, Teizo Asano, Masato Sano, Tomohiro Tanaka, Hiroyuki Harada, Takuya Mizuno, Tomokazu Ohishi, Manabu Kawada, Mika K. Kaneko, Yukinari Kato

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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 (mAb), clone EMab-134 (mouse IgG1, kappa), which specifically detects both hEGFR and dog EGFR (dEGFR). The defucosylated mouse IgG2a version 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.

Original languageEnglish
Pages (from-to)53-58
Number of pages6
JournalMonoclonal Antibodies in Immunodiagnosis and Immunotherapy
Volume41
Issue number2
DOIs
Publication statusPublished - 2022 Apr

Keywords

  • ADCC
  • antitumor activity
  • CDC
  • EGFR
  • mouse-dog chimeric antibody

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