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

D A Heideman, P J Snijders, M E Craanen, E Bloemena, C J Meijer, S G Meuwissen, V W van Beusechem, H M Pinedo, D T Curiel, H J Haisma, W R Gerritsen

Research output: Contribution to journalArticleAcademicpeer-review

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)342-51
Number of pages10
JournalCancer gene therapy
Volume8
Issue number5
DOIs
Publication statusPublished - May 2001

Keywords

  • Adenocarcinoma
  • Adenoviridae
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • DNA Primers
  • Epithelial Cell Adhesion Molecule
  • Esophageal Neoplasms
  • Gene Targeting
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Immunoenzyme Techniques
  • Journal Article
  • Paraffin Embedding
  • RNA, Messenger
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms
  • Tumor Cells, Cultured

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