title: An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer.
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.
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.|Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors: Mei-Ying
authors: MY
authors: Liao
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Jun-Kai
authors: JK
authors: Lai
authors: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors: Mark Yen-Ping
authors: MY
authors: Kuo
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Ruei-Min
authors: RM
authors: Lu
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Cheng-Wei
authors: CW
authors: Lin
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Ping-Chang
authors: PC
authors: Cheng
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors: Kang-Hao
authors: KH
authors: Liang
authors: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Han-Chung
authors: HC
authors: Wu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000071858:Epithelial Cell Adhesion Molecule; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods; D014803:Vitamin B Complex / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D014803:Vitamin B Complex; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: EpCAM; cancer therapy; colorectal carcinoma; targeting imaging; therapeutic antibody