Use of Tissue-specific Expression of the Herpes Simplex Virus Thymidine Kinase Gene to Inhibit Growth of Established Murine Melanomas following Direct Intratumoral Injection of DNA

Richard G. Vile, Ian R. Hart

Research output: Contribution to journalArticle

241 Scopus citations

Abstract

We report here the use of the 5’ flanking region of the murine tyrosinase gene to direct expression of the herpes simplex virus thymidine kinase (tk) gene specifically to murine melanoma cells, whilst not permitting expression in a range of other cell types. Expression of the herpes simplex virus tk gene from the tyrosinase promoter in melanoma cells rendered them sensitive to killing by ganciclovir (100% cell death of a ^-expressing B16 clone after 12 days in culture at 1 mg/ml ganciclovir). We also observed a substantial bystander killing effect when expressing cells were mixed with nontransfected parental B16 cells. When transfected murine melanoma cells expressing tk were injected into syngeneic mice both their tumorige-nicity and experimental metastatic potential were abrogated completely when the mice were treated with ganciclovir (27 of 28 mice treated with water developed progressively growing tumors versus 1 of 30 in the gan-ciclovir-treated group). Direct injection of the tk gene under control of the tyrosinase promoter into established tumors in mice, followed by treatment with ganciclovir, led to significant reductions in resultant tumor size relative to the size of tumor developing in mice treated with water (median tumor weight, 1.65 g versus 2.75 g). Therefore, direct transfer of recombinant genes by injection of DNA can significantly reduce established tumor burden in vivo.

Original languageEnglish (US)
Pages (from-to)3860-3864
Number of pages5
JournalCancer research
Volume53
Issue number17
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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