Anti‑EGFR monoclonal antibody 134‑mG2a exerts antitumor effects in mouse xenograft models of oral squamous cell carcinoma

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

doi:10.3892/ijmm.2020.4700

Anti‑EGFR monoclonal antibody 134‑mG2a exerts antitumor effects in mouse xenograft models of oral squamous cell carcinoma

Authors:
- 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
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Affiliations: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8575, Japan, Institute of Microbial Chemistry (BIKAKEN), Microbial Chemistry Research Foundation, Numazu‑shi, Shizuoka 410‑0301, Japan, Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113‑8510, Japan
Published online on: August 10, 2020 https://doi.org/10.3892/ijmm.2020.4700
Pages: 1443-1452
Copyright: © Hosono et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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