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

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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
Publication statusPublished - 10 Apr 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Dong, Y., Wen, P., Manome, Y., Parr, M., Hirshowitz, A., Chen, L., Hirschowitz, E. A., Crystal, R., Weichselbaum, R., Kufe, D. W., & Fine, H. A. (1996). In vivo replication-deficient adenovirus vector-mediated transduction of the cytosine deaminase gene sensitizes glioma cells to 5-fluorocytosine. Human Gene Therapy, 7(6), 713-720.