Abstract
Augmented delivery of cytokine-expressing DNA plasmids to subcutaneous tumors has been demonstrated to result in a level of enhanced anti-tumor activity. One delivery enhancement method which has been evaluated is in vivo electroporation (EP), a contact-dependent delivery technique where electric pulses are hypothesized to augment the transfer of DNA into cells and tissues through the induction of temporary cell membrane pores. Previous work by members of our group, as well as others, has demonstrated the anti-tumor effects of DNA plasmids expressing the cytokines IL-12 and IL-15. In this report the potential anti-tumor activity of a relatively newly-described cytokine, IL-28, was measured when administered intratumorally as a DNA expression plasmid (designated pIL28) to established murine (B16.F10) melanoma tumors. The administration of the IL-28 expressing plasmid was performed through enhanced delivery methods. One method was EP and the other a non-contact dependent technique using a helium plasma stream. IL-28 is a member of the type III interferon family of cytokines that has been characterized as possessing potent anti-viral activity. This cytokine has been demonstrated to function as an adjuvant in small animal model vaccination protocols and stimulates CD8+ CTL responses. In addition, stimulation of anti-tumor activity has been demonstrated in several studies using IL-28. Based on these activities, it was hypothesized that this cytokine could, when delivered through a DNA expression plasmid, mediate anti-tumor activity. The results of this study indicated that enhanced delivery of pIL-28 resulted in attenuation of tumor growth, compared with non-enhanced delivery. Of note, this is the first proof-of-concept experiment, of our knowledge, documenting the ability of a non-contact dependent helium plasma-based delivery method to mediate the enhancement of an anti-tumor effect by a cytokine-expressing DNA plasmid. This suggests the use of the helium plasma delivery method as an alternative or adjunctive method to EP for the effective delivery of agents that possess potential anti-tumor activity.