Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model

Anticancer Res. 2005 Jul-Aug;25(4):2757-60.

Abstract

Background: Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model.

Materials and methods: In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days.

Results: The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 microM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model.

Conclusion: The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.

MeSH terms

  • Acyclovir / pharmacokinetics
  • Acyclovir / pharmacology*
  • Adenoviridae / genetics
  • Animals
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Disease Models, Animal
  • Drug Synergism
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, Inbred C3H
  • Recombinant Proteins / pharmacology
  • Simplexvirus / enzymology
  • Simplexvirus / growth & development
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Transduction, Genetic
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • Interleukin-2
  • Recombinant Proteins
  • Thymidine Kinase
  • Acyclovir