Epithelial cell adhesion molecule (
EpCAM) is a type I transmembrane
glycoprotein, which is highly expressed on
tumor cells. As
EpCAM plays a crucial role in cell adhesion, survival, proliferation, stemness, and
tumorigenesis, it has been considered as a promising target for
tumor diagnosis and
therapy. Anti‑EpCAM
monoclonal antibodies (mAbs) have been developed and have previously demonstrated promising outcomes in several clinical trials. An anti‑EpCAM mAb, EpMab‑37 (mouse
IgG1, kappa) was previously developed by the authors, using the cell‑based immunization and screening method. In the present study, a defucosylated version of anti‑EpCAM mAb (EpMab‑37‑mG2a‑f) was generated to evaluate the antitumor activity against EpCAM‑positive cells. EpMab‑37‑mG2a‑f recognized EpCAM‑overexpressing CHO‑K1 (CHO/
EpCAM) cells with a moderate binding‑affinity [dissociation constant (KD)=2.2x10‑8 M] using flow cytometry. EpMab‑37‑mG2a‑f exhibited potent antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) for CHO/
EpCAM cells by murine splenocytes and complements, respectively. Furthermore, the administration of EpMab‑37‑mG2a‑f significantly suppressed CHO/
EpCAM xenograft
tumor development compared with the control mouse
IgG. EpMab‑37‑mG2a‑f also exhibited a moderate binding‑affinity (KD=1.5x10‑8 M) and high ADCC and CDC activities for a
colorectal cancer cell line (Caco‑2 cells). The administration of EpMab‑37‑mG2a‑f to Caco‑2 tumor‑bearing mice significantly suppressed
tumor development compared with the control. By contrast, EpMab‑37‑mG2a‑f never suppressed the xenograft
tumor growth of Caco‑2 cells in which
EpCAM was knocked out. On the whole, these results indicate that EpMab‑37‑mG2a‑f may exert antitumor activities against EpCAM‑positive
cancers and may thus be a promising therapeutic regimen for
colorectal cancer.