A novel anti‑EGFR monoclonal antibody (EMab‑17) exerts antitumor activity against oral squamous cell carcinomas via antibody‑dependent cellular cytotoxicity and complement‑dependent cytotoxicity

Takei,Junko; Kaneko,Mika  Kato; Ohishi,Tomokazu; Kawada,Manabu; Harada,Hiroyuki; Kato,Yukinari

doi:10.3892/ol.2020.11384

A novel anti‑EGFR monoclonal antibody (EMab‑17) exerts antitumor activity against oral squamous cell carcinomas via antibody‑dependent cellular cytotoxicity and complement‑dependent cytotoxicity

Authors:
- Junko Takei
- Mika Kato Kaneko
- Tomokazu Ohishi
- Manabu Kawada
- Hiroyuki Harada
- Yukinari Kato
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Affiliations: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Aoba‑ku, Sendai, Miyagi 980‑8575, Japan, Institute of Microbial Chemistry (BIKAKEN), Numazu, 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, Bunkyo‑ku, Tokyo 113‑8510, Japan
Published online on: February 10, 2020 https://doi.org/10.3892/ol.2020.11384
Pages: 2809-2816
Copyright : © Takei et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases; it is a transmembrane receptor involved in cell growth and differentiation. EGFR homodimers or heterodimers in combination with other HER members, such as HER2 and HER3, activate downstream signaling cascades in many types of cancer, including oral squamous cell carcinoma (OSCC). The present study produced novel anti‑EGFR monoclonal antibodies (mAbs) possessing antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC), and investigated antitumor activity. Mice were immunized with an EGFR‑overexpressed glioblastoma cell line, LN229 (LN229/EGFR), after which ELISA was performed using recombinant EGFR. mAbs were subsequently selected according to their efficacy for LN229/EGFR, as determined via flow cytometry. After determining the subclass of mAbs, the EMab‑17 (IgG2a, kappa) clone exhibited ADCC and CDC activities against two OSCC cell lines, HSC‑2 and SAS. Furthermore, EMab‑17 exerted antitumor activities against mouse xenograft models using HSC‑2 and SAS, indicating that EMab‑17 may be used in an antibody‑based therapy for EGFR‑expressing OSCC.

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