Available Drug Helps Prevent Breast Cancer Recurrence

Ontak boosts body's defense against tumor's return

THURSDAY, June 9, 2005 (HealthDay News) -- Using a drug already on the market, researchers say they can block key immune system cells that actually promote breast cancer recurrence. The therapy should re-arm the body's defenses against malignancy's return, they report.

"We used a drug which is an interleukin-2 immunotoxin," said lead researcher Keith Knutson, assistant professor of immunology at the Mayo Clinic College of Medicine, Rochester, Minn. The drug, Ontak (denileukin diftitox), is currently approved by the U.S. Food and Drug Administration to treat cutaneous T-cell lymphomas.

"What we found is the IL-2 immunotoxin doesn't kill tumors directly but it kills regulatory T-cells," Knutson said. And that, in turn, boosted the overall immune system functioning, he said.

The researchers, from the Mayo Clinic and the University of Washington, Seattle, presented their findings Thursday at the Department of Defense's Era of Hope Breast Cancer Research Program meeting in Philadelphia.

"We know that breast cancer is recognized by the immune system," Knutson said. "But a block in immunity occurs and the tumor continues to grow. We've found one potential block and a strategy to reduce the effect of that block."

"The block is an immune cell, the regulatory T-cell," he said.

Regulatory T-cells, also called suppressor T-cells, control the magnitude of the immune system response. While researchers have known about these cells for more than 30 years, "what's new is that in these breast cancers [studied], we found the regulatory T-cells are able to block the immune response," Knutson said.

"By killing them off, we let the immune system do what it was supposed to do in the first place," Knutson explained.

In the study, Knutson's team injected mice with human breast cancer cells, producing one group with early-stage cancer and another with late-stage malignancy. They treated half of each group with the IL-2 immunotoxin for 17 days while the other half served as untreated controls.

The researchers then monitored cancer progression in the animals for a total of 50 days, Knutson said.

They found that the immunotoxin delayed the growth of tumors in animals with early-stage cancers and slowed the growth of tumors in both early- and late-stage malignancies. Ontak also reduced tumor size in the treated group compared to controls. The tumors in the early-stage treated mice were 90 percent smaller than the nontreated controls with early-stage cancers, and 79 percent smaller in the treated late-stage group compared to the untreated late-stage controls.

The researchers then removed the tumors from the animals and exposed them to the immunotoxin. This had no effect, "so we know the drug itself isn't acting on the tumor, it is acting on the immune system," Knutson said.

At 50 days out, the treated mice were still successfully fighting off the tumors, Knutson added.

Eventually, he said, the therapy might be used to activate the immune system after a patient has undergone breast cancer treatment, to prevent relapse.

"We know that normal therapies like chemo, surgery and radiation don't kill all the tumor cells -- that is why patients relapse," he said. "If we can activate the immune system to control the residual tumor cells that are left, they can go on for an extended period of time, controlling tumor growth."

A cancer expert from the City of Hope National Medical Center in Duarte, Calif., praised the study. "These data are very interesting and hypothesis-generating," said Dr. Robert Morgan, a staff physician in the division of medical oncology and therapeutics research at the City of Hope.

"For many years, patients and oncologists have wondered why the immune mechanism is ineffective in preventing tumor development, growth and metastasis formation," he said. "These data suggest that the tumors themselves are affecting the immune system. This is early but promising research which will need to be confirmed in human trials."

In other presentations at the meeting, researchers from the University of New Mexico School of Medicine in Albuquerque reported that a new test that identifies genetic changes in breast tissue that appear normal could help predict relapse in breast cancer. They used an assay which measures the DNA content of telomeres -- protein complexes that cap off the end of chromosomes -- that are altered in tumors.

The investigators defined telomeres with a DNA content of less than 70 percent as tumor-like. In one study, they found this value predicted relapse in seven of 12 women whose breast cancer returned. It also predicted tumor suppression in 12 of 13 who remained cancer-free. The test must be refined before it is ready for widespread use, the researchers said.

In a third study, researchers at the University of Maryland School of Medicine in Baltimore reported that a special device can control the "scatter" of the electron beam used in radiation therapy. This effectively lowers the amount of radiation to less than 25 percent of the current dose, they said. The advanced beam device, which is expected to reduce complications such as long-term skin reactions, received a patent in April but requires further study, the research team said.

More information

To learn more about breast cancer, visit the American Cancer Society.

SOURCES: Keith Knutson, Ph.D., senior associate consultant, assistant professor, Mayo Clinic College of Medicine, Rochester, Minn.; Robert Morgan, M.D., staff physician, Division Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, Calif.; June 9, 2005, presentations, Department of Defense's Era of Hope Breast Cancer Research Program meeting, Philadelphia
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