OncoSec Medical Inc (ONCSQ)

[hankd112]

4:30PM - 4:45PM Gene Electrotransfer of IL-15/IL-15Ra as an Effective Immunotherapy in a Mouse Melanoma Model
SPEAKER

Dr. Richard Heller
Director and Professor, Frank Reidy Research Center for Bioelectrics

ABSTRACT

Richard Heller, Cathryn M. Lundberg, Niculina Burcus, and Shawna A. Shirley
1Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508 2Medical Diagnostics and Translational Sciences, Old Dominion University, Norfolk, VA 23508

Gene electrotransfer (GET) is a reliable and effective physical method for in vivo delivery of plasmid DNA (pDNA). Several pre-clinical and clinical studies have utilized GET to deliver genes for cancer therapy. It is particularly attractive for use in anti-cancer cytokine therapy as it does not incur the side effects associated with conventional protein cytokine therapy. Delivery of plasmids encoding cytokines directly to tumors has been shown by our lab and others to induce not only local immune response, but a systemic one as well. Previously we have shown that using GET to deliver interleukin-15 (IL-15) to mouse melanoma resulted in long term-tumor regression and survival of a percentage of treated animals after challenge. In the current study we have enhanced this anti-tumor activity by delivering both IL-15 and its soluble receptor IL-15Ra.

GET was used to deliver a plasmid encoding both IL-15 and its soluble receptor IL-15Ra to established B16.F10 tumors. Multiple delivery protocols were utilized to establish varying levels of gene expression. Plasmids expressing either IL-15 alone or IL-15Ra only were used as controls. Tumor volume was monitored for changes over a period of 9 weeks. Mice that were observed to be tumor free were then challenged with B16.F10 cells on the opposite flank and monitored for an additional 50 days. In separate experiments, protection was examined using a metastatic model. Over the course of the experiment, samples were collected for histology, IL-15 expression and cytokine analysis. Tumor regression and long- term survival in a larger percentage of animals was observed when GET was used to deliver the plasmid expressing both IL-15 and IL-15Ra compared to delivery of plasmid containing IL-15 only or simultaneous delivery of separate plasmids expressing IL-15 and IL-15Ra. After challenge, mice that were treated with the IL-15/IL-15Ra plasmid showed protection in 70% of the original treated group compared to only 30% of the group that received IL-15 only and 20% in the group that received the genes on separate plasmids. These results demonstrate that using GET to deliver IL-15/IL-15Ra a local and systemic anti- tumor immune response can be generated in a melanoma model.




http://www.isdv.org/2014/schedule/2014-dna-vaccine-conference