Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity against Breast Cancer in Mouse Xenograft Model

Teizo Asano
ORCID logo ,
Hiroyuki Suzuki
* ORCID logo ,
Guanjie Li
,
Tomokazu Ohishi
ORCID logo ,
Manabu Kawada
,
Takeo Yoshikawa
ORCID logo ,
Tomohiro Tanaka
,
Mika K. Kaneko
,
Yukinari Kato
* ORCID logo
Version 1 : Received: 11 October 2022 / Approved: 12 October 2022 / Online: 12 October 2022 (10:08:42 CEST)

A peer-reviewed article of this Preprint also exists.

Asano, T.; Tanaka, T.; Suzuki, H.; Li, G.; Ohishi, T.; Kawada, M.; Yoshikawa, T.; Kaneko, M.K.; Kato, Y. A Defucosylated Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity in Xenograft Model. Antibodies 2022, 11, 74. https://doi.org/10.3390/antib11040074 Asano, T.; Tanaka, T.; Suzuki, H.; Li, G.; Ohishi, T.; Kawada, M.; Yoshikawa, T.; Kaneko, M.K.; Kato, Y. A Defucosylated Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity in Xenograft Model. Antibodies 2022, 11, 74. https://doi.org/10.3390/antib11040074

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 IgG1, kappa). In this study, we investigated the antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against an EpCAM‐expressing breast cancer cell line (BT-474). EpMab-37-mG2a-f recognized BT-474 cells with a moderate binding-affinity [a dissociation constant (KD): 2.9x10-8 M] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for BT-474 cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the BT-474 xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities against the BT-474 xenograft, and could provide valuable therapeutic regimen for the breast cancers.

Keywords

EpCAM; breast cancer; antitumor activities; antibody‐dependent cellular cytotoxicity

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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