ElectroChemotherapy
...electric pulses temporarily increase the cell membrane permeability, allowing the chemotherapeutic agent to efficiently enter and kill the cancer cells...
Due to the inherent inability of cancer therapeutics to efficiently cross cell membranes, higher and higher doses of these anti-cancer agents must be used in the hope of demonstrating a therapeutic benefit in cancer patients. To counter this, OncoSec's ElectroChemotherapy approach utilizes cell targeted electric pulses to temporarily increase the cells' membrane permeability and therefore allow the chemotherapeutic agent to efficiently enter and kill the cancer cells. This therapy combines the OncoSec Medical System (OMS) and its electroporation devices (generator and applicator) with an approved anti-cancer drug (bleomycin) to safely and efficiently treat solid tumors. The goal for this therapy is to directly kill the cancerous cells of both the tumor and its margins while preserving the healthy tissue surrounding the tumor and avoiding the detrimental cosmetic, functional and other side effects of surgery, radiation systemic chemotherapy and other emerging therapies.
The OMS was described in the previous section. Following is a description of the anti-cancer drug, bleomycin.
Bleomycin: a Proven Anti-Cancer Medicine Gets a New Opportunity
The goal of chemotherapy is to kill cancer cells with high efficiency, while keeping serious toxic side effects, such as fatigue, vomiting, or a decline in certain blood and immunity parameters, as low as possible. The mechanism of action of most chemotherapeutic agents is to enter the tumor cells and then either damage the DNA in order to induce cell death or prevent the DNA's function or repair.
Bleomycin is a well-established anti-cancer drug which is approved, readily available for human use in most countries, and not prohibitively expensive. Unfortunately, when administered conventionally by intravenous infusion into systemic distribution in the body it is not particularly effective for the treatment of malignant tumors due to its inefficient entry into cancer cells. Moreover, used in this high dose fashion it is toxic, resulting in significant side effects.
...Electroporation has been shown to enhance the ability of bleomycin to kill tumor cells by 6,000 to 8,000 fold. Through the use of targeted, local administration, the dose of bleomycin has been reduced to 1/20th of that normally used for systemic chemotherapy...
Some characteristics of bleomycin delivered using electroporation include:
- When bleomycin is injected directly into a tumor and the tumor is then immediately exposed to electroporation, the effectiveness of the drug is increased significantly.
- Through extensive in vitro and in vivo studies and after testing over 20 chemotherapeutic drugs in a broad variety of tumor types with and without electroporation, the combination of intratumorally injected bleomycin and electroporation was consistently the most effective cytotoxic agent.
- While bleomycin demonstrated excellent cancer killing efficacy through objective tumor responses (complete or partial elimination of tumors), the significant reduction in the therapeutic doses utilized also resulted in lower systemic drug distribution and corresponding side effects.
How it Works
The increase in efficacy (by several thousand-fold) is based on the ability of electroporation to form temporary "pores" or nano-holes in the cell membrane. The resulting membrane holes allow bleomycin to efficiently and rapidly enter the target cell. Shortly after the electroporation has caused the drug to enter the target cell, the pores close and trap the bleomycin inside the cell where it acts catalytically to destroy the cancer cell's nucleic acids (DNA and potentially RNA) via an apoptotic or "cell-suicide" mechanism. In addition to more drug entering the cancer cell, it has been shown that tumors injected with bleomycin retain the drug much longer when electroporated as compared to non-electroporated tumor cells. Both of these factors significantly increase the cancer cell killing ability of bleomycin.
Minimal Dosage Required
Using the OncoSec Medical System, physicians are able to reduce the standard treatment dose of bleomycin to 1 unit per cm3 of tumor structure. For the vast majority of tumors, this dose will be well below the level which would be given during conventional systemic chemotherapy treatment and comfortably under the mandated maximal lifetime dose of 400 units.
Preserves Healthy Tissue
A significant added advantage of bleomycin delivered via the OncoSec Medical System is its preferential killing of rapidly dividing cancerous cells. Most conventional cancer treatments cannot distinguish between cancerous and normal cells. In the case of surgical excision, a margin of healthy tissue surrounding the tumor is always removed in order to eliminate potentially cancerous outlier cells. The impact of removing additional non-cancerous tissue can lead to both functional and/or cosmetic detrimental outcomes. The OncoSec Medical System's ability to effectively and efficiently treat cancer cells yet preserve healthy normal tissue provides important benefits in terms of organ function, appearance and general quality of life.
Approved Medication
While bleomycin is widely approved in North America, Europe and Asia for systemic anti-cancer use, it is also available to be used for intratumoral injection in Germany, Switzerland, Austria, the UK, France, Italy, and Belgium. OncoSec believes that drug agency approval for intratumoral injection of bleomycin in other countries will be a matter of regulatory filing steps and not extensive technical reviews. OncoSec is executing these steps to ensure all required labeling and governing approvals for intratumoral use of bleomycin are in place in targeted countries. Finally, OncoSec will be working with both global and local suppliers of bleomycin to ensure stable, cost effective supply agreements are also in place.
A Less Invasive Therapy at Less Cost
Surgery can often involve significant post-treatment care and extensive surgical reconstruction. Chemotherapy and radiation therapy, to the extent these are used to control tumor growth, have many side effects that can range from limiting the treatments to even disqualifying the therapeutic approach in many patients. As an effective local tumor treatment, bleomycin delivered with electroporation can reduce or avoid these often debilitating side effects.
As an example, patients who have oral/lingual tumors and are treated with the OncoSec Medical System are less likely to lose their tongue or portions of their jaw, as is the case with the standard therapy, surgery. Head and neck patients who undergo surgery often need reconstruction of the resected areas, further complicating recovery and increasing treatment costs. Some ElectroChemotherapy treatments can be performed on an outpatient basis, reducing the incidences of ill health associated with hospital stays from extensive cancer surgery. Furthermore, pharmacoeconomic data analysis to date suggests that a typical treatment using the OncoSec Medical System will cost significantly less than surgery.
Demonstrated Effectiveness
It has been demonstrated with extensive pre-clinical and clinical data from Phase 1 through 4 clinical trials that OncoSec's ElectroChemotherapy approach is both safe and highly effective in eradicating solid tumors including head & neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, and liver and pancreatic cancers. In all of these clinical applications, bleomycin is injected into or applied to the surface of the cancerous tumor and electroporation pulses are delivered directly to the target tissue. The resulting cancer cell destruction is quickly observable, with the wound healing completely resolving in a matter of weeks.
Examples of OMS ElectroChemotherapy Treatments
Example of Head & Neck Cancer Patient Treatment: ElectroChemotherapy of squamous cell carcinoma
Lateral Tongue Cancer | Electrochemotherapy |
1 day post electrochemotherapy | 4 weeks post electrochemotherapy |
Example of Skin Cancer Patient Treatment: ElectroChemotherapy of basal cell carcinoma
Pre-Treatment | 30 Days Post-Treatment |
90 Days Post-Treatment | 120 Days Post-Treatment |