A Defucosylated Anti-EpCAM Monoclonal Antibody (EpMab-37-mG-f) Exerts Antitumor Activity in Xenograft Model

Overview

Journal Antibodies (Basel)

Date 2022 Dec 22

PMID 36546899

Authors

Teizo Asano

Tomohiro Tanaka

Hiroyuki Suzuki

Guanjie Li

Tomokazu Ohishi

Manabu Kawada

Takeo Yoshikawa

Mika K Kaneko

Yukinari Kato

Affiliations

Soon will be listed here.

Abstract

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti-EpCAM monoclonal antibody (EpMab-37; mouse IgG, kappa). In this study, we investigated the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG-type of EpMab-37 (EpMab-37-mG-f) against a breast cancer cell line (BT-474) and a pancreatic cancer cell line (Capan-2), both of which express EpCAM. EpMab-37-mG-f recognized BT-474 and Capan-2 cells with a moderate binding-affinity [apparent dissociation constant (): 2.9 × 10 M and 1.8 × 10 M, respectively] by flow cytometry. EpMab-37-mG-f exhibited ADCC and CDC for both cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG-f significantly suppressed the xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG-f exerts antitumor activities and could provide valuable therapeutic regimen for breast and pancreatic cancers.

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