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Enhanced Gene Therapy Boosts Anti-Tumor Response

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(Arun Kulshreshtha, Wikimedia Commons)

3 April 2017. Gene therapies delivered with electronic pulses were shown in lab mice to increase production of natural immune-system proteins and reduce melanoma, or advanced skin cancer, tumors. A team from the biotechnology company OncoSec Medical Inc. in San Diego presented its findings today at a meeting of American Association of Cancer Research in Washington, D.C.

Melanoma is an aggressive type of skin cancer, which while not as common as basal cell and squamous cell skin cancers, is more likely to spread to other parts of the body. American Cancer Society expects more than 87,000 people in the U.S. to develop melanoma in 2017, leading to some 9,700 deaths. If melanoma is caught and treated early, before it spreads or metastasizes, the 5-year survival rate is 98 percent. After the cancer spreads to other parts of the body, however, the 5-year survival rate drops to 16 percent.

OncoSec develops solid tumor cancer treatments that harness the the cancer fighting capabilities of the interleukin 12, or IL-12, a natural protein in the body that fights off invading pathogens, but can also be directed at cancer. When used by itself as a therapy, however, interleukin 12 can cause serious unexpected adverse effects, often as a result of its promoting production of other proteins in the body.

OncoSec overcomes this problem by simultaneously aiming electroporation, or mild electronic pulses, at the tumor as DNA plasmids with genes producing interleukin 12 are injected into the tumor. These pulses, says the company, weaken the tumor cell membranes, making them less resistant to interleukin 12, allowing for smaller and safer amounts of the protein. OncoSec is testing its technology in clinical trials on its own and with other cancer treatments on several kinds of skin cancer, including melanoma, and triple-negative breast cancer.

The company’s treatments are also designed to generate a systemic, or whole-body, response by “training” the patient’s T-cells in the immune system to recognize the cancer, wherever it may spread. To enhance this capability, OncoSec researchers evaluated gene therapies to produce a variation of interleukin 12 known as IL-12 p70, which the team administered with electroporation to the tumors. IL-12 p70 combines the two main components of interleukin 12 and is considered desirable for systemic treatments.

In tests in lab mice induced with melanoma, the gene therapies successfully reduced the size of primary, or original, tumors, with the higher the dose given the mice, the more shrinkage in their tumors. In addition, the results show increased production of CD8 T-cells targeting specific melanoma cells that spread in the body. The findings also show tumors elsewhere in the body shrunk, suggesting a strong systemic response.

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