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.