An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer
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Mei-Ying Liao1,2,*, Jun-Kai Lai1,*, Mark Yen-Ping Kuo2, Ruei-Min Lu1, Cheng-Wei Lin1, Ping-Chang Cheng1, Kang-Hao Liang1, Han-Chung Wu1,3
1Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan
3Genomics Research Center, Academia Sinica, Taipei, Taiwan
*These authors have contributed equally to this work
Han-Chung Wu, e-mail: [email protected]
Keywords: colorectal carcinoma, EpCAM, therapeutic antibody, targeting imaging, cancer therapy
Received: March 12, 2015 Accepted: July 24, 2015 Published: August 06, 2015
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.
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