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
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Comparative Study
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Evaluation Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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DNA, Recombinant / administration & dosage*
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DNA, Recombinant / therapeutic use
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Electroporation*
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Fibrosarcoma / immunology
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Fibrosarcoma / pathology
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Fibrosarcoma / therapy*
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Genetic Therapy / methods*
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Genetic Vectors / administration & dosage*
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Genetic Vectors / therapeutic use
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Immunologic Memory
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Injections, Intradermal
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Injections, Intralesional
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Interferon-gamma / biosynthesis
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Interferon-gamma / blood
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Interferon-gamma / genetics
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Interleukin-12 / biosynthesis
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Interleukin-12 / blood
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Interleukin-12 / genetics
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Interleukin-12 / therapeutic use*
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Male
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Mice
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Mice, Inbred A
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Neoplasm Transplantation
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Neoplasms, Multiple Primary / immunology
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Neoplasms, Multiple Primary / pathology
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Neoplasms, Multiple Primary / therapy
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Plasmids / administration & dosage*
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Plasmids / genetics
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Plasmids / therapeutic use
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Random Allocation
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Secondary Prevention
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Soft Tissue Neoplasms / immunology
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Soft Tissue Neoplasms / pathology
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Soft Tissue Neoplasms / therapy*
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Specific Pathogen-Free Organisms
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Subcutaneous Tissue
Substances
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DNA, Recombinant
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Interleukin-12
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Interferon-gamma