Discovery May Lead to Vaccine

 

ORLANDO, Fla., Apr 04, 2001 (United Press International via COMTEX) -- A team of researchers at the University of California, Berkley, discovered a protein on prostate cancer cells that they say could be the first potential target for a vaccine.

At a press briefing Tuesday, the researchers, led by immunologist Dr. James Allison, a professor of molecular and cell biology, explained that the protein, called an antigen, alerts the immune system to the presence of a prostate tumor, ushering in an army of powerful immune cells to destroy it.

The scientists worked backwards, identifying the protein in mice bred with a predisposition toward prostate cancer, and then locating the correlating gene on the human genome. It had never been identified before. If the protein is unique to prostate cancer cells, it could lead to earlier diagnosis of the disease and pave the way for development of vaccine therapy, Allison said.

"This is the first prostate cancer antigen found, Allison said. He announced the findings at Experimental Biology 2001, an international meeting of basic medical researchers sponsored by the Federation of American Societies for Experimental Biology. "The hope is twofold," he said. "First, knowing what the specific target of the immune system is, we can do some very direct studies of whether it is a prognosticator of favorable outcome of disease. And second, we can start thinking about using the antigens to develop a specific vaccine."

Prostate cancer is the second leading cause of cancer death in men, after lung cancer.

According to Dr. Marston Linehan, chief of the Urologic Oncology Branch at the National Cancer Institute, in Bethesda, Md., the work "is very exciting" because a similar antigen targeting technique developed against melanoma has already led to one vaccine, "so we know the technique works."

He told UPI, "These are very exciting strategies at developing an immunologic defense against cancer. That it was detected in mice that had become potentially resistant to therapy is another highlight. This is a very tight group of researchers and they do good work."

Linehan also said that such an approach should prove far less traumatic to a man with prostate cancer because it narrows the area of treatment to just those cancerous cells rather than the entire organ. "This will be significantly less devastating," he noted.

Allison and his colleagues found the cancer antigen in the strain of mice prone to prostate cancer by treating the mice with a therapy they discovered for unleashing the immune system against prostate tumors -- then looking for those mice that successfully fought off the tumor.

From one mouse survivor, they isolated immune cells, called T cells, which play the most important role in protecting the body from cancer, and used them to pluck the antigen out of the many proteins in prostate cells. The treatment they used is now in Phase I human trials at two hospitals in California.

Once they found the protein, and then the gene for this antigen, they looked in databases and found a corresponding gene in human prostate. The corresponding human prostate antigen is the protein that could be used to generate a vaccine against prostate cancer.

The goal of such vaccines is to generate a massive T cell response strong enough to eliminate the tumor, even if it has disseminated throughout the body. To date, only a handful of antigens unique to tumors have been found, limiting the usefulness of vaccination against cancer. Melanoma, an often deadly type of skin cancer, is the exception, with many known antigens, and promising vaccine therapies now undergoing clinical trials.

"This is the first mouse we've looked at, so we have lots more work to do both in prostate and other kinds of cancer, including mammary cancer," Allison said. "I'm sure this is not the only antigen."

(Reported by Kurt Samson in Washington, D.C.)