IL-12 gene therapy using an electrically mediated nonviral approach reduces metastatic growth of melanoma.
Interleukin-12 (IL-12) has been evaluated in both preclinical and clinical immunotherapy protocols as a potential therapy for melanoma. However, delivery of IL-12 in the form of recombinant protein can result in severe toxicity, and gene therapy has had limited success against B16.F10 murine melanoma. This study investigated the therapeutic effect of delivering a plasmid encoding IL-12 followed by electroporation on primary and secondary tumors. Three treatments of intratumoral (i.t.) plasmid injection and electroporation resulted in 80% of mice with B16.F10 melanoma tumors being tumor free for >100 days (cure). The "cured animals" were resistant to challenge with B16 cells. In a separate experiment, B16 cells were injected on the opposite flank of the treated tumor on the day of treatment. Eighty-seven percent of control mice developed a distant tumor while only 43.8% of mice receiving two or three i.t. electroporation treatments developed a distant tumor. For examination of tumor development in the lungs, mice were injected intravenously with B16.F10 cells then treated with i.m. injections of plasmid with or without electroporation. Only 37.5% of mice receiving i.m. injections and electroporation developed nodules in the lungs compared to 87.5% of mice in the no-treatment group. The results show that administration of a plasmid encoding IL-12 with electroporation has a therapeutic effect on primary tumors as well as distant tumors and metastases.
Lucas
M Lee
ML
Department of Medical Microbiology and Immunology, University of South Florida, Tampa, Florida 33612, USA.
Heller
Richard
R
D020533:Angiogenesis Inhibitors / Q000235:genetics*; D000818:Animals; D018274:Electroporation / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D018664:Interleukin-12 / Q000235:genetics*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008546:Melanoma, Experimental / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D018664:Interleukin-12