OncoSec Medical, a San Diego-based company developing DNA-based intratumoral cancer immunotherapies, has entered a sponsored research agreement (SRA) with the University of Washington to evaluate the immunologic mechanisms of intratumoral DNA IL-12 electroporation.

Dr. I. Nicholas Crispe, MBBS, Ph.D., a professor in the department of immunology at the University of Washington, will be Principal Investigator. Using a novel liver cell isolation approach, Crispe has demonstrated that different types of liver cells have the capacity to present antigens, which likely contributes to hepatic immunosuppressive mechanisms. In this SRA, Crispe will apply these techniques to the B16 melanoma tumor model to not only better understand the systemic mechanisms of intratumoral DNA IL-12 electroporation (ImmunoPulse), but also to potentially identify other molecular targets that might combine with IL-12 to enhance immune response.

Crispe said, “We are focusing on taking the insights we have learned from studies of the basic biology of immune tolerance, and translating them directly to a model of human cancer. Although our initial target is malignant melanoma, we believe it is likely that data from these studies will be directly applicable to other cancers.”

Interleukin-12 (IL-12) is a potent inflammatory cytokine that regulates multiple aspects of the immune system; in particular, it initiates both innate and adaptive immune responses. IL-12 is a key driver of the cascade of biological events that ultimately lead to T-cell-specific killing of cancer cells. Moreover, cytokines and chemokines induced by this pathway also increase the recruitment of inflammatory T-cells into tumors.

ImmunoPulse is a proprietary investigational electroporation device that delivers plasmid IL-12 DNA directly into tumors. By locally delivering and expressing IL-12, ImmunoPulse has shown in clinical studies to elicit anti-tumor immune activity, which has led not only to local tumor regression, but also to systemic anti-tumor regression, while mitigating toxicities typically observed with systemic administration of IL-12. Preliminary interim data from OncoSec’s ongoing phase II study in melanoma provide evidence that local delivery of IL-12 by electroporation increases the production of cytokines such as IFN-γ, resulting in increased expression of genes related to the processes required for cytotoxic CD8+ T cells to recognize and kill cancer cells.