1. ¹Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, FL, USA
2. ²Center for Molecular Delivery, University of South Florida College of Medicine, Tampa, FL, USA
3. ³Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
4. ⁴Department of Pathology and Laboratory Medicine, University of South Florida College of Medicine, Tampa, FL, USA

Correspondence: Dr KE Ugen, Department of Medical Microbiology and Immunology, MDC 10, University of South Florida College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL 33612, USA. E-mail: kugen@hsc.usf.edu

Received 10 January 2006; Revised 10 February 2006; Accepted 22 April 2006; Published online 9 June 2006.

Abstract

In vivo electroporation has been used to efficiently deliver drugs and 'therapeutic' genes to tumors, including melanoma lesions. This study reports on the effect of intratumoral delivery of an optimized DNA plasmid expressing interleukin-15 (pIL-15) on established murine melanoma tumors. IL-15 has been demonstrated to have a pivotal role in the function of memory CD8+ T cells and natural killer cells, which are critical for tumor immunosurveillance. In this study, C57BL/6 mice were injected with B16.F10 melanoma cells and randomized into different experimental groups: untreated (P-V-E-), treated with pIL-15 (P+) or backbone plasmid (V+), with or without electroporation (E+ or E-). Treatment was performed intratumorally with 50 g of plasmid on days 0, 4 and 7 and tumor volume/size, tumor regression and long-term survival were measured. At day 100 after initiation of treatment, the percentage of mice surviving with complete tumor regression in the P-V+E+, P+V-E-, P+V-E+ and P-V-E- treatment groups were 0, 12.5, 37.5 and 0%, respectively. These results demonstrate the ability of pIL-15 to mediate B16 melanoma regression, with the effect being significantly enhanced by electroporative delivery. This is the first description of the ability of a naked DNA plasmid expressing IL-15 to alone mediate complete regression of B16 melanoma tumors and underscores the potential clinical use of these plasmids for the treatment of malignant tumors when delivered with in vivo electroporation.