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

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

doi:10.3892/or.2020.7808

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

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

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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 (IgG_2a, 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 K_Dfor EpMab-16 in SAS and HSC-2 OSCC cells were assessed via flow cytometry at 1.1×10^-8and 1.9×10^-8M, 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.

Original language	English
Pages (from-to)	2517-2526
Number of pages	10
Journal	Oncology Reports
Volume	44
Issue number	6
DOIs	https://doi.org/10.3892/or.2020.7808
Publication status	Published - 2020 Dec

Keywords

ADCC
Antitumor activity
CDC
EpCAM
Monoclonal antibody
Oral cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3892/or.2020.7808

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@article{734c0b55f90747d1b0c855033b284b22,

title = "Anti-EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas",

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 KDfor EpMab-16 in SAS and HSC-2 OSCC cells were assessed via flow cytometry at 1.1×10-8and 1.9×10-8M, 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.",

keywords = "ADCC, Antitumor activity, CDC, EpCAM, Monoclonal antibody, Oral cancer",

author = "Kaneko, {Mika K.} and Tomokazu Ohishi and Junko Takei and Masato Sano and Takuro Nakamura and Hideki Hosono and Miyuki Yanaka and Teizo Asano and Yusuke Sayama and Hiroyuki Harada and Manabu Kawada and Yukinari Kato",

note = "Funding Information: We would like to thank Ms. Saori Handa, Ms. Saki Okamoto, and Mr. Yu Komatsu (Department of Antibody Drug Development, Tohoku University Graduate School of Medicine) for technical assistance of in vitro experiments, and Ms. Akiko Harakawa (Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation) for technical assistance of animal experiments. Funding This research was supported in part by the Japan Agency for Medical Research and Development (AMED) under grant nos. JP20am0401013 (to YK), JP20am0101078 (to YK), and JP20ae0101028 (to YK), and by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) grant no. 17K07299 (to MKK), grant nos. 19K07705 (to YK), and 20K16322 (to MS). Publisher Copyright: {\textcopyright} 2020 Spandidos Publications. All rights reserved.",

year = "2020",

month = dec,

doi = "10.3892/or.2020.7808",

language = "English",

volume = "44",

pages = "2517--2526",

journal = "Oncology Reports",

issn = "1021-335X",

publisher = "Spandidos Publications",

number = "6",

}

TY - JOUR

T1 - Anti-EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas

AU - Kaneko, Mika K.

AU - Ohishi, Tomokazu

AU - Takei, Junko

AU - Sano, Masato

AU - Nakamura, Takuro

AU - Hosono, Hideki

AU - Yanaka, Miyuki

AU - Asano, Teizo

AU - Sayama, Yusuke

AU - Harada, Hiroyuki

AU - Kawada, Manabu

AU - Kato, Yukinari

N1 - Funding Information: We would like to thank Ms. Saori Handa, Ms. Saki Okamoto, and Mr. Yu Komatsu (Department of Antibody Drug Development, Tohoku University Graduate School of Medicine) for technical assistance of in vitro experiments, and Ms. Akiko Harakawa (Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation) for technical assistance of animal experiments. Funding This research was supported in part by the Japan Agency for Medical Research and Development (AMED) under grant nos. JP20am0401013 (to YK), JP20am0101078 (to YK), and JP20ae0101028 (to YK), and by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) grant no. 17K07299 (to MKK), grant nos. 19K07705 (to YK), and 20K16322 (to MS). Publisher Copyright: © 2020 Spandidos Publications. All rights reserved.

PY - 2020/12

Y1 - 2020/12

N2 - 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 KDfor EpMab-16 in SAS and HSC-2 OSCC cells were assessed via flow cytometry at 1.1×10-8and 1.9×10-8M, 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.

AB - 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 KDfor EpMab-16 in SAS and HSC-2 OSCC cells were assessed via flow cytometry at 1.1×10-8and 1.9×10-8M, 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.

KW - ADCC

KW - Antitumor activity

KW - CDC

KW - EpCAM

KW - Monoclonal antibody

KW - Oral cancer

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U2 - 10.3892/or.2020.7808

DO - 10.3892/or.2020.7808

M3 - Article

C2 - 33125138

AN - SCOPUS:85094946788

SN - 1021-335X

VL - 44

SP - 2517

EP - 2526

JO - Oncology Reports

JF - Oncology Reports

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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