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

Oncotarget
Mei-Ying LiaoHan-Chung Wu

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.

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Citations

Dec 16, 2018·International Journal of Molecular Sciences·Toni NunesAnne Janin
Jan 11, 2019·Journal of Cellular Physiology·Seyed Muhammad Yahyazadeh MashhadiAmirhosein Sahebkar
Jun 9, 2020·Cancer Metastasis Reviews·Olivier GiresPatrick A Baeuerle
Nov 10, 2018·Journal of Immunology Research·Qing ZhangJunnian Zheng
Oct 27, 2020·Frontiers in Immunology·Eleonora PonterioTobias Longin Haas
Apr 16, 2020·Free Radical Biology & Medicine·Doria BoulghobraCyril Reboul
May 18, 2016·ACS Applied Materials & Interfaces·Kiki C AndreeLeon W M M Terstappen
Sep 30, 2021·Irish Journal of Medical Science·Xiaoqian WuZhichao Jiang

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Datasets Mentioned

BETA
DI164282
GM882764

Methods Mentioned

BETA
surgical resection
nuclear translocation
flow cytometry
immunoprecipitation
xenografts
ELISA
phage display
transfection
biopsies
FCS

Software Mentioned

BIAevaluation
IVIS
ExPASy Proteomics Server
MacDNAsis

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