Augmentation of antitumor effect of adenovirus-mediated CD suicide gene therapy by cotransfer of interleukin 2 gene in melanoma-bearing mice

Chin Med J (Engl). 1999 Feb;112(2):162-5.

Abstract

Objective: To investigate the antitumor effect of combined adenovirus encoding E. coli cytosine deaminase (AdCD) and adenovirus encoding murine interleukin 2 (AdIL-2) on murine melanoma.

Methods: C57BL/6 mice were inoculated s.c. with B16F10 melanoma cells and 3 days later received injections of AdCD and/or AdIL-2 at the site of tumor inoculation followed by administration of 5-flurocytosine (5FC) 300 mg/kg per day for 10 days.

Results: Mice receiving AdCD/5FC/AdIL2 therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5FC, AdIL2, AdlacZ/5FC, or PBS. Immunological analysis illustrated that combined treatment could enhance NK activity and CTL activity. Flow cytometry demonstrated that AdCD/5FC/AdIL2 therapy increased the expression of MHC-1 and CD80 molecules on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly after the combined therapy.

Conclusions: Our data showed that combined transfer of CD suicide gene and IL-2 gene could inhibit the tumor growth more significantly. The increased specific and non-specific antitumor immunity might be responsible for the enhanced therapeutic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics
  • Animals
  • Cytosine Deaminase
  • Escherichia coli / genetics
  • Female
  • Flucytosine / therapeutic use*
  • Gene Transfer Techniques
  • Genes, Tumor Suppressor
  • Genetic Therapy*
  • Interleukin-2 / genetics*
  • Interleukin-2 / therapeutic use
  • Male
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Nucleoside Deaminases / genetics*
  • Nucleoside Deaminases / therapeutic use

Substances

  • Interleukin-2
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase