Local and systemic antitumor effect of intratumoral and peritumoral IL-12 electrogene therapy on murine sarcoma

Cancer Biol Ther. 2009 Nov;8(22):2114-22. doi: 10.4161/cbt.8.22.9734. Epub 2009 Nov 5.

Abstract

Soft tissue sarcomas pose a challenge for successful treatment with conventional therapeutic methods, therefore newer therapeutic approaches are considered. In this study, we evaluated the antitumor effect of IL-12 electrogene therapy (EGT) on murine SA-1 fibrosarcoma. The therapeutic plasmid was injected either intratumorally into subcutaneous SA-1 nodules or intradermally into the peritumoral region. We achieved a remarkable local and systemic antitumor effect with both approaches after single plasmid DNA application, with significant intratumoral and systemic production of IL-12 and IFNgamma. Intratumoral IL-12 EGT resulted in over 90% complete response rate of the treated tumors with 60% of cured mice being resistant to challenge with SA-1 tumor cells. Peritumoral EGT resulted in a lower complete response rate (16%), with significant growth delay of remaining tumors. Both therapies also resulted in significant inhibition of growth of untreated tumors, growing simultaneously at a distant site. These data suggest that IL-12 EGT may be useful in the treatment of soft tissue sarcomas, exerting a local and systemic antitumor effect.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Recombinant / administration & dosage*
  • DNA, Recombinant / therapeutic use
  • Electroporation*
  • Fibrosarcoma / immunology
  • Fibrosarcoma / pathology
  • Fibrosarcoma / therapy*
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / therapeutic use
  • Immunologic Memory
  • Injections, Intradermal
  • Injections, Intralesional
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / blood
  • Interleukin-12 / genetics
  • Interleukin-12 / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred A
  • Neoplasm Transplantation
  • Neoplasms, Multiple Primary / immunology
  • Neoplasms, Multiple Primary / pathology
  • Neoplasms, Multiple Primary / therapy
  • Plasmids / administration & dosage*
  • Plasmids / genetics
  • Plasmids / therapeutic use
  • Random Allocation
  • Secondary Prevention
  • Soft Tissue Neoplasms / immunology
  • Soft Tissue Neoplasms / pathology
  • Soft Tissue Neoplasms / therapy*
  • Specific Pathogen-Free Organisms
  • Subcutaneous Tissue

Substances

  • DNA, Recombinant
  • Interleukin-12
  • Interferon-gamma