An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer

Mei Ying Liao, Jun Kai Lai, Mark Yen Ping Kuo, Ruei Min Lu, Cheng Wei Lin, Ping Chang Cheng, Kang Hao Liang, Han Chung Wu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Epithelial cell adhesion molecule (EpCAM) is known to be overexpressed in epithelial cancers associated with enhanced malignant potential, particularly colorectal carcinoma (CRC) and head and neck squamous cell carcinoma (HNSCC). However, it is unknown whether progression of malignance can be directly inhibited by targeting EpCAM. Here, we have generated five novel monoclonal antibodies (mAbs) against EpCAM. One of these anti-EpCAM mAbs, EpAb2-6, was found to induce cancer cell apoptosis in vitro, inhibit tumor growth, and prolong the overall survival of both a pancreatic cancer metastatic mouse model and mice with human colon carcinoma xenografts. EpAb2-6 also increases the therapeutic efficacy of irinotecan, fluorouracil, and leucovorin (IFL) therapy in a colon cancer animal model and gemcitabine therapy in a pancreatic cancer animal model. Furthermore, EpAb2-6, which binds to positions Y95 and D96 of the EGF-II/TY domain of EpCAM, inhibits production of EpICD, thereby decreasing its translocation and subsequent signal activation. Collectively, our results indicate that the novel anti-EpCAM mAb can potentially be used for cancer-targeted therapy.

Original languageEnglish
Pages (from-to)24947-24968
Number of pages22
JournalOncotarget
Volume6
Issue number28
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Cancer therapy
  • Colorectal carcinoma
  • EpCAM
  • Targeting imaging
  • Therapeutic antibody

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Liao, M. Y., Lai, J. K., Kuo, M. Y. P., Lu, R. M., Lin, C. W., Cheng, P. C., Liang, K. H., & Wu, H. C. (2015). An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer. Oncotarget, 6(28), 24947-24968. https://doi.org/10.18632/oncotarget.4453