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Attacking Tumors Before They Develop

Prototype vaccine prevents breast cancer formation in mice.
“We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines prevent polio and measles in children.”

Cleveland Clinic researchers have gotten favorable results from a potential breast cancer vaccine in animal models. Their research could eventually lead to the first vaccine to prevent breast cancer formation in women over 40 years old and those at high risk for the disease. 
The researchers found that a single vaccination with the antigen α-lactalbumin prevents breast cancer tumors from forming in mice, while also inhibiting the growth of already existing tumors. Human trials could begin within the next year. Results were published online May 30 and will appear in the June 10 issue of Nature Medicine.
 
“We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines prevent polio and measles in children,” says Vincent Tuohy, the study’s principal investigator and an immunologist in Cleveland Clinic’s Lerner Research Institute Department of Immunology. “If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer.”
 
In the study, genetically cancer-prone mice were vaccinated—half with a vaccine containing α-lactalbumin and half with a vaccine that did not contain the antigen. None of the mice vaccinated with α-lactalbumin developed breast cancer, while all of the other mice did.
 
The U.S. Food and Drug Administration has approved two cancer-prevention vaccines to date, one against cervical cancer and one against liver cancer, both of which target viruses rather than cancer formation itself. Cancer presents researchers with a problem not posed by viruses.
 
In terms of developing a preventive vaccine, cancer presents a dilemma not posed by viruses. While viruses are recognized as foreign invaders by the immune system, cancer is an over-development of the body's own cells. Trying to vaccinate against this cell over-growth would effectively be vaccinating against the recipient's own body, destroying healthy tissue.
 
The key, Tuohy says, is to find a target within the tumor that is not typically found in a healthy person. In the case of breast cancer, Tuohy and his research team targeted α-lactalbumin — a protein that is found in the majority of breast cancers, but is not found in healthy women, except during lactation. Therefore, the vaccine can accelerate a woman's immune system to target α-lactalbumin to stopping tumor formation without damaging healthy breast tissue.
 
Breast cancer is the most common cancer worldwide according to the World Health Organization with 1.4 million new cases annually and 458,000 deaths. The National Cancer Institute estimates that there were 192,000 new diagnoses of breast cancer in the United States in 2009 and close to 41,000 deaths.
 
The strategy would be to vaccinate women over 40 when breast cancer risk begins to increase and pregnancy becomes less likely. If a woman becomes pregnant after being vaccinated, she would experience breast soreness and would likely have to choose not to breast feed. For younger women with a heightened risk of breast cancer, the vaccine may be an option to consider instead of prophylactic radical mastectomy.
 
“Most attempts at cancer vaccines have targeted viruses, or cancers that have already developed,” said Joseph Crowe, director of the Breast Center at Cleveland Clinic. “Dr. Tuohy is not a breast cancer researcher, he's an immunologist, so his approach is completely different—attacking the tumor before it can develop. It’s a simple concept, yet one that has not been explored until now.”
 
Tuohy believes that the findings of this study go beyond breast cancer, providing insight into the development of vaccines to prevent other types of cancer. The results show that the antigen used in a cancer vaccine must be over-expressed in the majority of targeted tumors and it must not be found in normal tissue, except under specific, avoidable conditions (such as lactation).
 
 

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