Cancer vaccine a step closer; Immune system fights prostate disease in Hopkins experiment; 'We were astounded'


Scientists at the Johns Hopkins Oncology Center have shown for the first time that an experimental vaccine made from a patient's tumor can spur the immune system to fight his prostate cancer.

The vaccine was tested in a group of men who had their prostates surgically removed but whose disease had spread to adjacent lymph nodes. This is the first sign of metastatic prostate cancer, which proves fatal in the vast majority of cases.

Dr. Jonathan Simons, who led the study, said that further research will be needed to see whether the vaccine is capable of bringing cancer into remission -- or better yet, of curing the disease. But he said the experiment was an important step, showing that a vaccine can trigger the immune system to fight cancer in the manner that it fights infection.

"For years, people have said there's no way to turn the immune system against prostate cancer," Simons said. "We were astounded to find that every part of the immune system was alerted and turned on."

Simons said the experiment produced a more comprehensive attack than anyone had expected, provoking not only the release of T-cells, as he had hoped, but also the production of antibodies against cancer. Both are key weapons of the immune system.

As scientists eye the future of cancer therapy, many consider vaccines to be among the two or three treatments that show the most promise. Vaccines are also being tried against other cancers, including melanoma and brain cancer.

In theory, vaccines would be more effective and less toxic than conventional therapies. Vaccines are generally viewed as a weapon that could be used with chemotherapy, radiation and surgery.

Despite the encouraging results, Simons said experiments like his should be viewed with caution.

"We absolutely do not have a cure by any stretch," he said.

Prostate cancer strikes about 330,000 men in the United States each year. New therapies are needed for the 40,000 men who die each year because their cancer has spread beyond the prostate to lymph nodes, bones and vital organs. It is the fourth-leading cancer killer in the United States, after cancers of the lung, colon and breast.

In the experiment, reported in this month's Cancer Research, Hopkins scientists injected a genetically altered cancer vaccine into 11 patients whose cancer had spread despite the removal of their prostate. Each vaccine was custom-made from the patient's tumor.

Scientists chopped up the tumors and grew them on laboratory culture dishes. They inserted a gene, called GM-CSF, which produces a protein that alerts tissues to the presence of a foreign substance. The gene exists in all cells but is turned off in cancer cells: a key reason, according to some scientists, that cancer normally spreads with impunity.

The vaccine was irradiated to prevent cancer cells from growing further and injected into the thigh. In the weeks that followed, the scientists observed a wide-ranging immune response in the patients.

"The gene we used to turn on the immune system is so good that it activates everything," said Dr. William Nelson, who was involved in the study.

Scientists ran out of vaccine after giving patients a series of shots, a limitation of vaccines made from a patient's tumor.

In a subsequent experiment, researchers manufactured a "generic" vaccine, using more diffuse tumors from a patient who died several years ago. In that experiment, scientists have much more vaccine on hand and have found declining prostate specific antigen (PSA) levels in some patients, stable ones in others. A blood test measures levels of PSA, a substance that usually rises in the presence of cancer.

John Willey, a 54-year-old cancer patient from Poolesville, had his prostate removed six years ago. After surgery, he learned that cancer had spread to a lymph node. His PSA level began to rise but fell after Willey received several infusions of vaccine. Later, it rebounded, leading to a second round of vaccine.

"I have not had a precipitous drop in my PSA since then," he said. "But I have stayed even."

Willey said he has no idea whether the vaccine will benefit him but is eager to participate in the research. "The strongest thing that appealed to me was that this seemed to be attacking the cancer in a way that could kill it," he said. "I'm more than happy to work with doctors to develop something that might someday cure prostate cancer."

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