Gene Therapy Showing Promise in Fighting Melanoma

Article originally published in September, 1999

MADISON - In treating dogs for a highly aggressive form of melanoma, a University of Wisconsin-Madison research team is having success with a new cancer vaccine that could benefit human cancer-fighting efforts.

Professor Gregory MacEwen and research scientist Gary Hogge, of the UW-Madison School of Veterinary Medicine, have developed a method of gene therapy that helps the animal's immune system recognize and attack cancer cells. In the September issue of the journal Human Gene Therapy, the researchers reported the vaccine helped some animals live longer and shrunk the tumor in about 20 percent of animals treated.

"This is important work with melanoma, because there currently are no other treatment alternatives," said MacEwen. "Melanoma is resistant to chemotherapy drugs, and surgery doesn't always help because melanoma's spread is so aggressive. We're trying to establish this as a standard of care."

The study details the treatment of 16 dogs that had advanced stages of melanoma that could not be successfully treated through surgery or drugs. The cases were referred to the UW-Madison school by veterinarians from around the country.

To develop the vaccine, the researchers began by surgically removing as much of the tumor as possible. They extracted and purified individual cells from the tumor and injected DNA into those cells that accelerated production of chemicals called cytokines. Cytokine molecules stimulate production of certain white blood cells in the body. The altered cells are then injected back into patients in the form of a vaccine.

The vaccine is administered with a "gene gun," a unique tool that helps scientists insert genetic material into cells. With air pressure, the gun can shoot millions of microscopic gold beads coated with DNA into cells, which are then injected back into the patient. In cells that are penetrated by the beads, the new genetic material becomes integrated into the cell and the cytokine is produced.

With this therapy, the animal's immune response is improved by the increase in cytokine production. The cytokines "train" the immune system to recognize and kill tumor cells, Hogge said.

Cancer vaccines and gene therapy, which have become widely studied in the past decade, could provide a new approach to fighting cancer with fewer side effects than chemotherapy or radiation therapy. This study is unique, Hogge said, because the gene therapy can produce a broad range of immune responses against surviving tumor cells in the patient.

"This is a way to trick the immune system and get the body to fight the tumor," Hogge said.

MacEwen said this study closely parallels work in human gene therapy to treat cancer, and provides additional information that benefits those projects. "We try to target a lot of the research we do so it will benefit the development and design of human clinical trials," he said.

Dogs provide a good model for understanding cancer in humans, MacEwen said, because of their large size and biological similarity. The causes and behaviors of cancers in humans and dogs are also very similar.

Melanoma is a common type of oral cancer in dogs. While oral melanoma is rare in humans, there are roughly 35,000 cases of melanoma skin cancer reported in America each year, and it remains one of the deadliest forms of cancer because of its ability to spread rapidly, MacEwen said.

### - Brian Mattmiller, (608) 262-9772