Anti-EGFR monoclonal antibody 134-mg2a exerts antitumor effects in mouse xenograft models of oral squamous cell carcinoma

Hideki Hosono, Junko Takei, Tomokazu Ohishi, Masato Sano, Teizo Asano, Yusuke Sayama, Takuro Nakamura, Miyuki Yanaka, Manabu Kawada, Hiroyuki Harada, Mika Kato Kaneko, Yukinari Kato

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermal growth factor receptor (EGFR), a transmembrane receptor and member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases, is a critical mediator of cell growth and differentiation. EGFR forms homo- or heterodimers with other HER family members to activate downstream signaling cascades in a number of cancer cells. In a previous study, the authors established an anti-EGFR monoclonal antibody (mAb), EMab-134, by immunizing mice with the ectodomain of human EGFR. EMab-134 binds specifically to endogenous EGFR and can be used to detect receptor on oral cancer cell lines by flow cytometry and western blot analysis; this antibody is also effective for the immunohistochemical evaluation of oral cancer tissues. In the present study, the subclass of EMab-134 was converted from IgG1 to IgG2a (134-mG2a) to facilitate antibody-dependent cellular cytotoxicity (Adcc) and complement-dependent cytotoxicity (cdc). The dissociation constants (Kds) of EMab-134 and 134-mG2a against EGFR-expressing cHO-K1 (cHO/EGFR) cells were determined by flow cytometry to be 3.2x10-9 M and 2.1x10-9 M, respectively; these results indicate that 134-mG2a has a higher binding affinity than EMab-134. The 134-mG2a antibody was more sensitive than EMab-134 with respect to antigen detection in oral cancer cells in both western blot analysis and immunohistochemistry applications. Analysis in vitro revealed that 134-mG2a contributed to high levels of Adcc and cdc in experiments targeting cHO/EGFR, HSc-2, and SAS cells. Moreover, the in vivo administration of 134-mG2a significantly inhibited the development of cHO/EGFR, HSc-2, and SAS mouse xenografts in comparison to the results observed in response to EMab-134. Taken together, the findings of the present study demonstrate that the newly-formulated 134-mG2a is useful for detecting EGFR by flow cytometry, western blot analysis and immunohistochemistry. Furthermore, the in vivo results suggested that it may also be useful as part of a therapeutic regimen for patients with EGFR-expressing oral cancer.

Original languageEnglish
Pages (from-to)1443-1452
Number of pages10
JournalInternational journal of molecular medicine
Volume46
Issue number4
DOIs
Publication statusPublished - 2020 Oct

Keywords

  • ADCC
  • Antitumor activity
  • CDC
  • EGFR
  • Monoclonal antibody
  • Oral cancer

ASJC Scopus subject areas

  • Genetics

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