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Selective gene delivery toward gastric and esophageal adenocarcinoma cells via EpCAM-targeted adenoviral vectors

Cancer Gene Therapy volume 8, pages 342–351 (2001)Cite this article

Abstract

Application of recombinant adenoviral vectors for cancer gene therapy is currently limited due to lack of specificity for tumor cells. For gastric and esophageal adenocarcinoma, we present here that the relative abundant expression of the primary adenovirus receptor, coxsackie/adenovirus receptor (CAR), on normal epithelium compared to carcinoma favors the transduction of the epithelium. As such, to achieve specific transduction of cancer cells, targeting approaches are required that ablate the binding of the virus to CAR and redirect the virus to tumor-specific receptors. By immunohistochemistry and reverse transcriptase polymerase chain reaction assays, we demonstrate a marked difference in expression of the human epithelial cell adhesion molecule (EpCAM) between normal and (pre)malignant lesions of the stomach and esophagus. Based on this, we explored the feasibility of using EpCAM to achieve gastric and esophageal adenocarcinoma selective gene transfer. Adenoviral vectors redirected to EpCAM using bispecific antibodies against the adenovirus fiber-knob protein and EpCAM specifically infected gastric and esophageal cancer cell lines. Using primary human cells, an improved ratio of tumor transduction over normal epithelium transduction was accomplished by the EpCAM-targeted vectors. This study thus indicates that EpCAM-targeted adenoviral vectors may be useful for gastric and esophageal cancer–specific gene therapy in patients. Cancer Gene Therapy (2001) 8, 342–351

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Acknowledgements

This study was supported by grants from the Dutch Digestive Diseases Foundation (WS 95-12), the National Institute of Health (R01 CA74242 and R01 HL50255), and the National Cancer Institute (N01 CO-97110). We thank the Department of Surgery of the University Hospital Vrije Universiteit, and the Departments of Surgery and Pathology of the Academic Medical Center, Amsterdam, the Netherlands, for their help to obtain resection specimens from patients with gastric and esophageal adenocarcinomas.

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Authors and Affiliations

  1. Department of Gastroenterology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    Daniëlle A M Heideman, Mikael E Craanen & Stefan G M Meuwissen

  2. Department of Pathology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    Daniëlle A M Heideman, Peter J F Snijders, Elisabeth Bloemena & Chris J L M Meijer

  3. Department of Medical Oncology, Division of Gene Therapy, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    Daniëlle A M Heideman, Victor W van Beusechem, Herbert M Pinedo, David T Curiel, Hidde J Haisma & Winald R Gerritsen

  4. Gene Therapy Center, University of Alabama, Birmingham, Alabama

    David T Curiel

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  1. Daniëlle A M Heideman
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  2. Peter J F Snijders
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  3. Mikael E Craanen
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  11. Winald R Gerritsen
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Correspondence to Daniëlle A M Heideman.

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Heideman, D., Snijders, P., Craanen, M. et al. Selective gene delivery toward gastric and esophageal adenocarcinoma cells via EpCAM-targeted adenoviral vectors. Cancer Gene Ther 8, 342–351 (2001). https://doi.org/10.1038/sj.cgt.7700313

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