Systemic IL-12 gene therapy for treating malignancy via intramuscular electroporation.
Interleukin 12 (IL-12) is effective in treating systemic microscopic malignancies by inducing T helper 1 (T(H)1) response, inhibiting angiogenesis, and triggering secondary cytokine production. Unfortunately, daily systemic administration of an acute dose of IL-12 protein is very costly and severely toxic. Here, a simple, economic, and less toxic approach, intramuscular administration of IL-12 gene, is provided for treating tumors in three tumor models. The results indicate that intramuscular administration of IL-12 encoding plasmid DNA via electroporation is a promising technology for treating systemic residual malignancies (less than 3-5 mm in diameter), as illustrated by the inhibition of tumor growth and lung metastases as well as the extension of survival rate. This approach is not effective in treating tumors larger than 3-5 mm in diameter.
Zhu
Shiguo
S
Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA.
Li
Shulin
S
D000818:Animals; D045744:Cell Line, Tumor; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000235:genetics; D053672:Electrochemotherapy / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000628:therapy*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics
D004274:DNA, Recombinant; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma