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.