Intramuscular electroporation delivery of IL-12 gene for treatment of squamous cell carcinoma located at distant site

Cancer Gene Therapy
E HannaS Li

Abstract

Gene therapy with IL-12 has been shown to elicit potent systemic antitumor response in a variety of tumors. Although direct intratumoral injection is the most commonly used delivery route for gene therapy of solid tumors, the skeletal muscle has been shown to be an ideal tissue for gene delivery to produce systemic gene expression. We have previously demonstrated that electroporation delivery of a reporter gene to muscle enhances the transfection efficiency and the level of gene expression by two to three logs. We report here that intramuscular (i.m.) injection of as little as 10 microg of the IL-12 DNA plasmid followed by electroporation prevents squamous cell carcinoma (SCCVII) tumor establishment in up to 40% of experimental animals and reduces the volume of established tumors by 75% compared to controls (P<.05). By comparison, there was no difference in tumor growth observed between IL-12 injection alone and injection of empty vector with or without electroporation. The induction of antitumor activity by i.m. electroporation delivery of the IL-12 gene is associated with an increase in IL-12 expression in muscle and serum. The level of IL-12 expression in muscle and serum was 1500 pg/tibialias muscle and 170 pg/mL serum, res...Continue Reading

Citations

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