Defucosylated anti-epidermal growth factor receptor monoclonal antibody 134-mG2a-f exerts antitumor activities in mouse xenograft models of dog epidermal growth factor receptor-overexpressed cells

Nami Tateyama, Ren Nanamiya, Tomokazu Ohishi, Junko Takei, Takuro Nakamura, Miyuki Yanaka, Hideki Hosono, Masaki Saito, Teizo Asano, Tomohiro Tanaka, Masato Sano, Manabu Kawada, Mika K. Kaneko, Yukinari Kato

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermal growth factor receptor (EGFR) is a type I transmembrane protein, which is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. EGFR is a crucial mediator of cell growth and differentiation and forms homodimers or heterodimers with other HER family members to activate downstream signaling cascades. We previously established an anti-human EGFR (hEGFR) monoclonal antibody (mAb), clone EMab-134 (mouse IgG1), by immunizing mice with the ectodomain of hEGFR. In this study, the subclass of EMab-134 was converted from IgG1 to IgG2a (134-mG2a) and further defucosylated (134-mG2a-f) to facilitate antibody-dependent cellular cytotoxicity (ADCC). Although 134-mG2a-f was developed against hEGFR, it was shown to cross-react with dog EGFR (dEGFR) using flow cytometry. The dissociation constant (KD) of 134-mG2a-f against dEGFR-overexpressed CHO-K1 (CHO/dEGFR) cells was determined by flow cytometry to be 3.3 × 10-9 M, indicating that 134-mG2a-f possesses a high binding affinity to dEGFR. Analysis in vitro revealed that 134-mG2a-f contributed to high levels of ADCC and complement-dependent cytotoxicity (CDC) in experiments targeting CHO/dEGFR cells. Furthermore, the in vivo administration of 134-mG2a-f significantly inhibited the development of CHO/dEGFR in comparison with the results observed in response to control mouse IgG. Taken together, the findings of this study demonstrate that 134-mG2a-f could be useful as part of a therapeutic regimen for dEGFR-expressing canine cancers.

Original languageEnglish
Pages (from-to)177-183
Number of pages7
JournalMonoclonal antibodies in immunodiagnosis and immunotherapy
Volume40
Issue number4
DOIs
Publication statusPublished - 2021 Aug 1
Externally publishedYes

Keywords

  • ADCC
  • CDC
  • EGFR
  • antitumor activity
  • monoclonal antibody

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Defucosylated anti-epidermal growth factor receptor monoclonal antibody 134-mG<sub>2a</sub>-f exerts antitumor activities in mouse xenograft models of dog epidermal growth factor receptor-overexpressed cells'. Together they form a unique fingerprint.

Cite this