In vivo replication-deficient adenovirus vector-mediated transduction of the cytosine deaminase gene sensitizes glioma cells to 5-fluorocytosine

Yonghe Dong, Patrick Wen, Yoshinobu Manome, Michael Parr, Ari Hirshowitz, Ling Chen, Edward A. Hirschowitz, Ronald Crystal, Ralph Weichselbaum, Donald W. Kufe, Howard A. Fine

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Viral vector-mediated transfer of chemosensitization genes represents a promising new approach to the treatment of cancer. Previous reports have demonstrated that transfection of the bacterial cytosine deaminase (cd) gene into mammalian cells can sensitize them to the otherwise nontoxic nucleoside, 5-fluorocytosine (5-FC). We now report that a replication-deficient adenovirus vector that transduces the cd gene (Ad.CMV-cd) highly sensitizes 9L gliosarcoma cells to 5-FC, and that gene transduction is associated with a potent bystander effect that is not dependent on direct cell-to-cell contact. Stereotactic injection of Ad.CMV-cd into established rat gliomas, followed by systemic administration of 5-FC in vivo, results in prolongation of survival.

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalHuman Gene Therapy
Volume7
Issue number6
DOIs
StatePublished - Apr 10 1996

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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