Electroporation Key to Skin Cancer Treatment
One in five individuals is likely to suffer from skin cancer at some point in their lives, and the numbers are steadily increasing. Despite advances that have been made in sunscreen technology and growing public awareness of the need for sunscreen, data that were reported in Dermatology Times found that the average U.S. lifetime risk of invasive melanoma has increased from 1 in 600 in 1960 to 1 in 50 in 2008. As baby boomers grow older, there is an added risk that skin cancer and other sold tumor cancers will loom larger in their lives.
Unfortunately, the treatment of solid tumor cancers—ranging from melanoma to Merkel cell carcinoma to cutaneous T-cell lymphoma—is a major challenge. For example, it is difficult to deliver potentially useful drugs into cells in a safe and effective way. Meanwhile, the use of surgery to remove tumors can potentially cause physical disfigurement, while the perils of traditional radiation therapy and chemotherapy are well known. In addition, all of these traditional treatments are only minimally effective on these aggressive types of skin cancer, especially in later stages of the disease.
There seems to be two principal avenues now for patients with advanced skin cancer: targeted, oncogene-directed therapy, and systemic immunotherapy. Generally speaking, however, many of the emerging treatments in these categories have drawbacks that potentially limit their broad-based use for the treatment of solid tumors and in-transit skin cancers—typically referred to as locoregional metastases. The benefit of immunotherapies is that they can produce durable responses in a small subset of patients from the treatment and appear to work in patients with both BRAF-mutant and BRAF-wild-type melanomas. The benefit of molecularly targeted therapies is that they produce a high level of tumor shrinkage and survival benefits in a large proportion of patients with BRAF-mutant melanomas. Those responses are likely short-lived—median of six to eight months progression-free survival—but for patients with symptomatic disease who need a response, the high degree of response is a major benefit. The question is to what extent these therapies are able to selectively destroy cancer cells. The concern being that they may be too aggressive for locoregional metastases and negatively impact patient safety. There is an opportunity for these treatment avenues to be more selective and less toxic.
The ideal approach to treating advanced skin cancers, e.g. solid tumor cancers, is to target the tumor locally without affecting any of the surrounding healthy tissue, to ensure that a drug or other therapeutic agent is immediately absorbed by the cancer cells and stimulating a desired immune response. OncoSec Medical Inc. has developed a delivery system, called the OncoSec Medical System (OMS), to address these challenges.
OMS works by applying a brief electric field to a living cell, causing a temporary opening of pores in the cell’s outer membrane. These pores close a few minutes after the electric field is discontinued. By creating these membrane pores, the cell’s permeability is temporarily increased 1000-fold, and a drug or other agent injected into the area can flow into the cell much more easily.
The OMS electroporation platform consists of a generator that creates a pulsed electric field, and a handheld applicator that includes a small hexagonal arrangement of electrode needles at its tip.
The OMS was designed to be used in a type of therapy known as ImmunoPulse, in which electroporation is used in tandem with a substance known to boost the human immune system against cancer cells, to locally deliver an immunotherapy. OncoSec’s lead drug candidate is DNA-based interleukin-12 (IL-12). In a Phase 1 clinical trial for metastatic melanoma, ImmunoPulse demonstrated both safety and efficacy, with 53% of patients exhibiting objective response and 16% of patients exhibiting complete regression.
In 2012, OncoSec launched three Phase 2 clinical trials using ImmunoPulse in three types of cancer—metastatic melanoma, Merkel cell carcinoma, and cutaneous T-cell lymphoma. In interim data from the Phase 2 melanoma trial, 95% of treated lesions showed some response to the treatment by day 39. This is the first time the medical community has seen such a broad application to several very lethal skin cancers with no or very limited treatment options.
In terms of treatment duration, one cycle of ImmunoPulse therapy takes one week, whereas two rival, locally injected immunotherapies take six weeks and up to 48 weeks per cycle, respectively. This difference in length of treatment afforded by ImmunoPulse is potentially significant because treatment length is intimately connected to patient quality of life.
Targeted cancer therapies, such as those currently under development at OncoSec Medical, offer a potential new approach to the treatment of solid tumor cancers.
About the author
Punit Dhillon is president and CEO of OncoSec Medical Inc., a biotechnology company developing its advanced-stage Oncology Medical System (OMS) ImmunoPulse therapy to treat skin cancer and other solid tumor cancers.