Local and systemic antitumor effect of intratumoral and peritumoral IL-12 electrogene therapy on murine sarcoma.
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.
Pavlin
Darja
D
University of Ljubljana, Veterinary Faculty Ljubljana, Ljubljana, Slovenia.
Cemazar
Maja
M
Kamensek
Urska
U
Tozon
Natasa
N
Pogacnik
Azra
A
Sersa
Gregor
G
D000818:Animals; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000627:therapeutic use; D018274:Electroporation; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000627:therapeutic use; D007156:Immunologic Memory; D007271:Injections, Intradermal; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009368:Neoplasm Transplantation; D009378:Neoplasms, Multiple Primary / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D011897:Random Allocation; D055502:Secondary Prevention; D012983:Soft Tissue Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013047:Specific Pathogen-Free Organisms; D040521:Subcutaneous Tissue
D004274:DNA, Recombinant; D018664:Interleukin-12; D007371:Interferon-gamma