Journal
CLINICAL CANCER RESEARCH
Volume 14, Issue 22, Pages 7367-7377Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-1016
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Funding
- NIH [HD48540, CA86306, CA009120, 2-T32-Al-07323]
- University of California at Los Angeles Jonsson Comprehensive Cancer Center flow cytometry core [CA016042]
- Iris Cantor Seed Grant, Giannini Family Foundation [U54 CA119367]
- Oppenheimer Family Foundation
- Center for the Prevention of Eye Disease
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Purpose: Endometrial cancer is the most common gynecologic malignancy. One promising biomarker is epithelial membrane protein 2 (EMP2), and its expression is an independent prognostic indicator for tumors with poor clinical outcome expression. The present study assesses the suitability of EMP2 as a therapeutic target. Experimental Design: Human monovalent anti-EMP2 antibody fragments were isolated from a human phage display library and engineered as bivalent antibody fragments (diabodies) with specificity and avidity to both EMP2 peptides and native cell-surface EMP2 protein. Diabodies were assessed using cell death and apoptosis assays. In addition, the efficacy of EMP2 diabodies on endometrial cancer tumors was determined using mouse xenograft models. Results: Treatment of human endometrial adenocarcinoma cell lines with anti-EMP2 diabodies induced significant cell death and caspase-3 cleavage in vitro. These responses correlated with cellular EMP2 expression and were augmented by progesterone, which physiologically induces EMP2 expression. In vivo, treatment of subcutaneous human xenografts of HEC-1A cell lines with anti-EMP2 diabodies suppressed tumor growth and induced cell death in the xenograft. Conclusions: These findings suggest that EMP2 may be a potential pharmacologic target for human endometrial cancer.
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