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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1530268

Novel human single-domain antibodies exert potent anti-tumor activity by targeting EGF-like repeat epitope of EpCAM

Provisionally accepted
Xiaofeng Zhou Xiaofeng Zhou *Zhifang Liu Zhifang Liu Weixiong Zhang Weixiong Zhang Lin Dai Lin Dai Tao Chen Tao Chen Zexiong Lin Zexiong Lin Henry Wei Henry Wei *Qi Qi Qi Qi *
  • Jinan University, Guangzhou, China

The final, formatted version of the article will be published soon.

    A fully human single-domain antibody (sdAb) for cancer therapy has many advantages compared with the conventional monoclonal antibody (mAb), represented by efficient penetration into tumors, no immunogenicity, as well as recognizing hidden epitopes that are inaccessible to mAb. EpCAM is an important cancer stem cell (CSC) marker overexpressed in many cancers and a pivotal target for diagnosis and therapy. Studies so far with the anti-EpCAM mAbs for cancer therapy showed limited anti-tumor effects, which highlights the need for the development of more efficacious anti-EpCAM antibody drug candidates. In this study, a critical EGF-like repeat epitope on the EpCAM extracellular domain was selected for screening a human sdAb library by phage display. Five fully human anti-EpCAM sdAbs were isolated and they specifically bound to the EpCAM peptide with selective interation with cancer cell lines, but not to 293T and 3T3 cells. Functional studies showed that they significantly inhibited cancer cell proliferation, migration, invasion, and induced their apoptosis. In addition, two sdAbs showed potent anti-prostate tumor effect in vivo. This study provides compelling evidence that targeting EpCAM for cancer treatment and demonstrates that the anti-EpCAM sdAbs developed here are potential therapeutics for cancer treatment.

    Keywords: EpCAM, antibody, Single-domain antibody, cancer stem cells, cancer therapy

    Received: 18 Nov 2024; Accepted: 24 Jan 2025.

    Copyright: © 2025 Zhou, Liu, Zhang, Dai, Chen, Lin, Wei and Qi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiaofeng Zhou, Jinan University, Guangzhou, China
    Henry Wei, Jinan University, Guangzhou, China
    Qi Qi, Jinan University, Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.