Researchers have shown that vaccinating mice with a modified form of a virus containing proteins from breast cancer cells can kill large breast cancer tumors and tumors that have spread to the lungs. The rodent model of cancer used in this study closely resembles a type of breast cancer seen in humans called HER2-positive. Although other cancer vaccines have shown activity in the treatment of very small tumors, their ability to influence large, established tumors, such as many HER2-positive breast cancers, has proven difficult. The study, led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared in the March 15, 2008, issue of Cancer Research.

Therapeutic cancer vaccines are intended to disrupt new or existing cancerous growth by stimulating the body's immune system so that it recognizes the cancer as an invader. These vaccines use certain protein molecules on the surface of cancer cells, such as the HER2 receptor protein, as the triggers to initiate an immune response.

The modified virus used as a vaccine in this study showed activity against ErbB2-positive tumors. The ErbB2 gene is known as HER2 in humans, and neu is its counterpart in mice. Approximately 20 percent to 25 percent of breast cancers in women are HER2-positive and tumors overexpressing the HER2 receptor protein are more aggressive and more likely to recur than tumors that do not overexpress the protein. Thus, the HER2 receptor protein is an important target.
"A therapeutic vaccine may offer an advantage over treatments, such as monoclonal antibodies, that target a single site on a cancer cell because it may induce the production of several different antibodies that can target multiple regions on a receptor, making it harder for the tumor to mutate and escape the effects of therapy," said Jay A. Berzofsky, M.D., Ph.D., of the Vaccine Branch at NCI's Center for Cancer Research (CCR).

The research team, led by Berzofsky, along with Jong Myun Park, Ph.D., and Masaki Terabe, Ph.D., of the Vaccine Branch, and John Morris, M.D., of the Metabolism Branch of the CCR, conducted a series of experiments studying the effectiveness of a vaccine containing a modified form of adenovirus, a type of virus that primarily affects the respiratory tract, that expresses portions of neu (Ad-neuECTM) in the treatment of breast cancer in mice. They also investigated the possible mechanism by which the vaccine induces the destruction of tumor cells.

To create their breast cancer model, the team induced tumors by injecting TUBO cells - a mouse mammary cancer cell line that highly expresses the neu receptor on its surface - under the skin in mice. The research team found that when the Ad-neuECTM vaccine and TUBO cells were injected at the same time, tumors did not develop. In another experiment, the vaccine was administered seven, 10, or 15 days after TUBO cells had been injected into mice, and tumors had formed. The researchers observed that the tumors were smaller seven days after vaccination; all the tumors had disappeared between 25 and 45 days after the mice were vaccinated. The mice remained tumor-free through the end of the study.

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