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Vaccine against HER2-positive breast cancer offers complete protection in lab
Date:9/14/2008

th antibodies and killer T cells.

"While HER2 receptors are not usually seen by the immune system when they are expressed at low level on the surface of normal cells, a sudden flood of receptors alerts the body to an invasion that needs to be eliminated," Wei said. "During that process, the immune system learns to attack cancer cells that display large numbers of these receptors."

They also used an agent that, for a while, suppressed the activity of regulatory T cells, which normally keeps the immune system from over-reacting. In the absence of regulatory T cells, the immune system responded much more strongly to the vaccine. Then, when the researchers implanted HER2-positive breast tumors in the animals, the cancer was eradicated.

"Both tumor cells that respond to current targeted therapies and those that are resistant to these treatments were eradicated," Wei said. "This may be an answer for women with these tumors who become resistant to the current therapies."

Wei's lab is the first to develop HER2 DNA vaccines, and this is the second such vaccine Wei and her colleagues have tested more extensively. The first, described in a study in 1999, formed the model of a vaccine now being tested by a major Pharmaceutical company in early phase clinical trials in the U.S. and in Europe in women with HER2-positive breast cancer.

In order to ensure complete safety, Wei says the current test vaccine uses HER2 genes that are altered so that they cannot be oncogenic. The receptors produced do not contain an "intracellular domain" the part of the receptor that is located just below the cell surface and transmits growth signals to the nucleus. The first vaccine was also safe, she says, but contained a little more of the native HER2 receptor structure. "With this vaccine, I am quite certain the receptor is functionally dead," she said.

"The greatest power of vaccination is protection against initial cancer development, a
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Contact: Jeremy Moore
Jeremy.moore@aacr.org
267-646-0557
American Association for Cancer Research
Source:Eurekalert

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