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 KD for EpMab-16 in SAS and HSC-2 OSCC cells were assessed via flow cytometry at 1.1×10−8 and 1.9×10−8 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.