ElectroImmunotherapy

OncoSec's ElectroImmunotherapy program uses the OncoSec Medical System (OMS) to deliver a DNA-based therapy intended to induce a host immune response capable of killing cancerous cells in both the targeted solid tumor and any cancer cells within the margin of predominantly healthy tissues surrounding the tumor. The objective of this program is to stimulate and recruit the body's immune system in order to provide a selective and effective local treatment and potentially a systemic treatment effect targeting distal (untreated remote) cancer cells.

OncoSec is developing the use of the OMS to deliver a DNA-based cytokine therapy to up-regulate and stimulate the host immune system to fight cancer cells. For example, interleukin-12 (IL-12) cytokine is a naturally occurring protein that is released by the body's immune cells to activate and increase the levels of circulating macrophages and cytotoxic T-cells to respond and eliminate not only foreign organisms infecting the host but also emerging cancerous cells. As a potential anti-cancer therapy, the introduction of pro-inflammatory cytokine proteins into the body has produced encouraging data. Unfortunately, the full utility of this approach has not been demonstrated due to inherent difficulties in either directly introducing into the body the IL-12 protein itself (toxicities) or in having the DNA encoding the protein delivered, taken up by the target cells and adequately expressed (efficient gene transfer) to the level required to bring about a therapeutic and sustained response against the cancer cells. OncoSec is developing a method of treatment that addresses these limitations.

To overcome the limitations posed by the direct administration of cytokines or the lack of cytokine expression via traditional gene therapy methods, OncoSec's ElectroImmunotherapy approach utilizes the OncoSec Medical System (OMS) to deliver into both the cancerous tumor and the margin of the tumor a plasmid DNA construct coded to produce the IL-12 protein. Delivery of the IL-12 gene with OMS electroporation results in the rapid and efficient uptake of the DNA into the electroporated cells. Following entry into the targeted cell, the plasmid DNA construct provides instructions to the cellular machinery to first produce and then secrete the IL-12 protein into the extracellular space where it brings about its intended immune function via the induction of adaptive and innate immune properties.

In a situation where the tumor cells have evaded detection by the immune system, they have gained the ability to maintain unregulated growth and further develop into clusters and eventually solid tumors. However, by utilizing the OMS delivery of IL-12 DNA to artificially facilitate the production and cellular release of IL-12 within the tumor, the host immune function can be stimulated to identify and eliminate the cancerous cells. The anti-tumor effectiveness of the IL-12 protein is due to the stimulation, proliferation and maturation of both cytotoxic T-cells and NK-cells and the production of IFN-, all of which result in the detection of the abnormal features of the cancer cells and the resulting destruction and elimination of those cells through conventional immune cell processes.

While the IL-12 immunotherapy is administered locally, initial evidence suggests that the resulting immune response produces both a local and a systemic effect against the recognized abnormal cells. If this evidence can be further validated, the DNA-based IL-12 immunotherapy would represent an important development in the treatment of both local and metastatic disease. OncoSec's most advanced immunotherapy program for the delivery of DNA IL-12 into a tumor via electroporation has demonstrated both safety and efficacy in a Phase 1 clinical trial in metastatic melanoma and is currently being advanced to enter a Phase 2 confirmatory study before the end of the year.