Slingluff team developing melanoma vaccine

By Nancy Hurrelbrinck

Scientists have discounted for decades the idea that the body's immune system can fight cancer, but the work of several U.Va. researchers is proving them wrong.

"Now there's a lot of evidence that immune responses to cancer do occur," said Craig L. Slingluff Jr., associate professor of surgery. "We're looking at the response of T-lymphocytes," white blood cells that can kill cells infected with a virus, as well as cancer cells.

"We can take blood from melanoma patients and generate a population of cells that can kill cells from their tumor," said Slingluff, who has been researching melanoma, a form of skin cancer, with microbiology professor Victor H. Engelhard and Donald F. Hunt, University Professor of Chemistry and Pathology.

"The big question is how these lymphocytes can exist in the body and not kill the cancer cells."

One answer: tumors can evade immune recognition by making substances that are immuno-suppressive, he said, adding that he has seen lymphocytes even in people with advanced disease.

Slingluff's team has been working with Interleukin-2, a growth factor for lymphocytes that the Food and Drug Administration (FDA) has approved for treating melanoma for a year.

"We can generate lymphocytes in a culture that kill tumor cells," he said, noting that when patients are given these cells back, fortified with interleukin-2, their tumors are shrunk as effectively or better than if they'd used chemotherapy.

"The problem is that it's a very time-intensive process," he said. "The patient can die in the time it takes to grow the cells. We want to treat people in the early stage of the disease, to stimulate a response in [them] that takes advantage of their immune system."

Ultimately, Slingluff's team hopes to develop a vaccine reliable enough to use in healthy people. "We have been trying to identify molecules on the surface of melanoma that the T-lymphocytes recognize so we can use those molecules to vaccinate people.'

Since 1991, they've identified four of these molecules and used them in vaccines that are currently being tested in three clinical trials, he said.

"It's very exciting to me to be able to offer these treatments. The standard treatment now is early surgery, then watch and wait," he said, adding that, for people with cancer that has spread to the lymph nodes, who are expected to die within five to 10 years, there's no treatment with significant impact.

Slingluff's team has set up a human immune therapy center to facilitate establishing immunology clinical trials. Colleagues are developing a protocol for a standard immunology therapy vaccine for colon cancer, and they want to start trials for breast and lung cancer vaccines, he said.

"A lot of clinicians taking care of patients want to offer new things," he said. "The issue is when to translate research into trials and deal with regulatory agencies" such as the FDA and several U.Va. committees.

They have gotten the process, which took two years eight years ago, down to six months.

"We expect that each cancer will eventually have its own vaccine," he said.