Anti‑EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas

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

doi:10.3892/or.2020.7808

Anti‑EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas

Authors:
- Mika K. Kaneko
- Tomokazu Ohishi
- Junko Takei
- Masato Sano
- Takuro Nakamura
- Hideki Hosono
- Miyuki Yanaka
- Teizo Asano
- Yusuke Sayama
- Hiroyuki Harada
- Manabu Kawada
- 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: October 13, 2020 https://doi.org/10.3892/or.2020.7808
Pages: 2517-2526
Copyright: © Kaneko et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The epithelial cell adhesion molecule (EpCAM) is a calcium‑independent, homophilic, intercellular adhesion factor classified as a transmembrane glycoprotein. In addition to cell adhesion, EpCAM also contributes to cell signaling, differentiation, proliferation, and migration. EpCAM is an essential factor in the carcinogenesis of numerous human cancers. In the present study, we developed and validated an anti‑EpCAM monoclonal antibody (mAb), EpMab‑16 (IgG2a, kappa), by immunizing mice with EpCAM‑overexpressing CHO‑K1 cells. EpMab‑16 specifically reacted with endogenous EpCAM in oral squamous cell carcinoma (OSCC) cell lines in flow cytometry and Western blot analyses. It exhibited a plasma membrane‑like stain pattern in OSCC tissues upon immunohistochemical analysis. The KD for EpMab‑16 in SAS and HSC‑2 OSCC cells were assessed via flow cytometry at 1.1x10‑8 and 1.9x10‑8 M, respectively, suggesting moderate binding affinity of EpMab‑16 for EpCAM. We then assessed whether the EpMab‑16 induced antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) against OSCC cell lines, and antitumor capacity in a murine xenograft model. In vitro experiments revealed strong ADCC and CDC inducement against OSCC cells treated with EpMab‑16. In vivo experiments on OSCC xenografts revealed that EpMab‑16 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that EpMab‑16 could be a promising treatment option for EpCAM‑expressing OSCCs.

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