June 2005
Mayo collaboration: Discovery blocks breast cancer growth, stimulates immunity
ROCHESTER, Minn. -- Mayo Clinic researchers today announced the discovery of a mechanism that blocks the body's natural ability to reject breast cancer. They also described an experimental therapy to remove that block. The findings were announced in a news conference at a major gathering of breast cancer specialists, the Era of Hope -- Department of Defense Breast Cancer Research Program meeting in Philadelphia.
The goal of the research is to prevent breast cancer recurrence in women who've already experienced remission of the disease. In cases where cancer has spread outside the breast, the 10-year relapse rate can be as high as 90 percent.
Mayo Clinic researchers -- collaborating with colleagues at the University of Washington -- showed that their experimental therapy to remove the block did not harm the immune system -- in fact, it boosted it. Mice that received the toxic injections that killed the immune system blockages had tumors that were one-tenth the size of mice that did not receive the injections.
Breast cancer researchers have known for years that the body's immune system is naturally poised to reject breast cancer -- but in breast cancer patients, something interferes with this rejection, allowing the cancer to grow unchecked. This new finding helps unlock that mystery and may lead to safer, gentler therapies.
"Evidence is emerging that some of the effects of chemotherapy are due to depleting T-regulatory (T-reg) cells," says Keith Knutson, Ph.D., the Mayo Clinic immunology researcher who led the study. "The strategy we use in our investigation may actually be a way to target the T-regs directly, without using the indirect route of chemotherapy. Depleting T-regulatory cells may boost natural immunity against breast cancer."
Significance of the Research
The Mayo Clinic and University of Washington collaborative study is the first to show these two new important aspects of breast cancer: - T-regulatory cells play a disease-promoting role in breast cancer.
- T-regs can be selectively and therapeutically eliminated without harming the immune response of white blood cells. Instead, blocking T-regs boosts natural immunity.
Dr. Knutson emphasized that further studies must validate these findings before they can be applied to human breast cancer patients. Even so, he says this is a welcome research advance because breast cancer is the most commonly diagnosed non-skin cancer in women. According to the National Breast Cancer Foundation, this year in the United States more than 211,000 women will be diagnosed with breast cancer and 43,300 will die from it.
About Immunotherapy and IL-2 Immunotoxin
Dr. Knutson is a specialist in the cutting-edge field of immunotherapy, and Mayo Clinic is a major immunotherapy research center (http://mayoresearch.mayo.edu/mayo/research/ciip/). Immunotherapy is the strategy that seeks to therapeutically harness the natural healing powers of the immune system and direct them against cancers and other diseases to improve treatment and minimize side effects.
The IL-2 immunotoxin used in Dr. Knutson's mouse study is based on a naturally occurring immune-system molecule that has been modified in the laboratory to specifically locate T-reg cells and kill them. The IL-2 immunotoxin is commercially available and currently approved for use by the U.S. Food and Drug Administration (FDA) to treat a different disease, cutaneous T-cell lymphoma.
The Experiment and its Findings
The researchers studied the effects of the IL-2 immunotoxin in two groups of about a dozen mice each. All mice were injected with invasive human breast cancer cells to produce one group with early stage minimal cancer and a second group with late-stage established cancer. These two cancer stage groups were then compared to control groups of mice injected with breast cancer but not treated with the IL-2 immunotoxin.
Results showed that at the end of the treatment cycle, the IL-2 immunotoxin: - significantly delayed the growth of tumors in animals with early stage, minimal tumors.
- slowed the growth of tumors in both early stage and late stage tumor groups.
- reduced mean tumor sizes as compared to controls. In the minimally diseased group, tumors were 90 percent smaller, and in the late-stage well-established group they were 79 percent smaller than those of the control group.
- produced tumor response that is dose dependent: more was better.
- worked through the immune system -- not directly on the tumor. Researchers discovered this by removing the tumors from the mice and treating the tumors with the IL-2 immunotoxin -- and saw no impact. This suggests the IL-2 immunotoxin needs the biological context of the immune system to be effective, not simple contact with tumor cells.
Collaboration and Support
In addition to Dr. Knutson, the following researchers from the University of Washington were part of the research team: Yushe Dang, Ph.D.; Hailing Lu, Ph.D.; Jason Lukas, M.D.; Bond Almand, M.D.; Ekram Makary, Ph.D.; Ehizoje Azeke; and Mary Disis, Ph.D. Their work was supported by the National Institutes of Health and Mayo Foundation.
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