The anti‑epithelial cell adhesion molecule (EpCAM) monoclonal antibody EpMab‑16 exerts antitumor activity in a mouse model of colorectal adenocarcinoma

Hideki Hosono, Tomokazu Ohishi, Junko Takei, Teizo Asano, Yusuke Sayama, Manabu Kawada, Mika K. Kaneko, Yukinari Kato

Research output: Contribution to journalArticlepeer-review

Abstract

The epithelial cell adhesion molecule (EpCAM), which is a calcium‑independent homophilic intercellular adhesion factor, contributes to cell signaling, differentiation, proliferation and migration. EpCAM is essential for carcino‑ genesis in numerous types of human cancer. The purpose of the present study was to establish an anti‑EpCAM monoclonal antibody (mAb) for targeting colorectal adenocarcinomas. Thus, an anti‑EpCAM mAb, EpMab‑16 (IgG2a, κ), was estab‑ lished by immunizing mice with EpCAM‑overexpressing CHO‑K1 cells, and validated using flow cytometry, western blot, and immunohistochemical analyses. EpMab‑16 reacted with endogenous EpCAM specifically in a colorectal adeno‑ carcinoma cell line as determined by flow cytometry and western blot analyses. Immunohistochemical analysis demon‑ strated that EpMab‑16 stained a plasma membrane‑like pattern in clinical colorectal adenocarcinoma tissues. The dissociation constant (KD) for EpMab‑16 in a Caco‑2 colorectal adenocarci‑ noma cell line determined by flow cytometry was 1.8x10‑8 M, suggesting moderate binding affinity of EpMab‑16 for EpCAM. Whether the EpMab‑16 induced antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) against Caco‑2 or antitumor activity was then assessed in a murine xenograft model. In vitro experiments revealed strong ADCC and CDC induction in Caco‑2 cells by EpMab‑16 treatment. In vivo experiments in a Caco‑2 xenograft model demonstrated that EpMab‑16 treatment significantly reduced tumor growth compared with that in mice treated with the control mouse IgG. These results suggested that EpMab‑16 may be a promising treatment option for EpCAM‑expressing colorectal adenocarcinomas.

Original languageEnglish
Article number12246
JournalOncology Letters
Volume20
Issue number6
DOIs
Publication statusPublished - 2020 Dec

Keywords

  • ADCC
  • Antitumor activity
  • CDC
  • Colorectal adenocarcinoma
  • EpCAM
  • Monoclonal antibody

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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