Vaccine against HER2-positive breast cancer offers complete protection in lab

[Guest guest]

http://www.wkyc.com/news/news_article.aspx?storyid=96530

Vaccine against HER2-positive breast cancer offers complete protection in

lab

Posted By: 1 day ago

PHILADELPHIA ? Researchers at Wayne State University have tested a breast

cancer vaccine they say completely eliminated HER2-positive tumors in mice,

even cancers resistant to current anti-HER2 therapy, without any toxicity.

The study, reported in the September 15 issue of Cancer Research, a journal

of the American Association for Cancer Research, suggests the vaccine could

treat women with HER2-positive, treatment-resistant cancer or help prevent

cancer recurrence. The researchers also say it might potentially be used in

cancer-free women to prevent initial development of these tumors.

HER2 receptors promote normal cell growth, and are found in low amounts on

normal breast cells. But HER2-positive breast cells can contain many more

receptors than is typical, promoting a particularly aggressive type of tumor

that affects 20 to 30 percent of all breast cancer patients. Therapies such

as trastuzumab and lapatinib, designed to latch on to these receptors and

destroy them, are a mainstay of treatment for this cancer, but a significant

proportion of patients develop a resistance to them or cancer metastasis

that is hard to treat.

This treatment relied on activated, own-immunity to wipe out the cancer,

says the study's lead investigator, Wei-Zen Wei, Ph.D., a professor of

immunology and microbiology at the Karmanos Cancer Institute.

" The immune response against HER2-positive receptors we saw in this study is

powerful, and works even in tumors that are resistant to current therapies, "

she said. " The vaccine could potentially eliminate the need to even use

these therapies. "

The vaccine consists of " naked " DNA ? Genes that produce the HER2 receptor ?

As well as an immune stimulant. Both are housed within an inert bacterial

plasmid. In this study, the researchers used pulses of electricity to

deliver the injected vaccine into leg muscles in mice, where the gene

produced a huge quantity of HER2 receptors that activated both 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, and that is our ultimate goal with this treatment, " Wei said.

© 2008 wkyc-TV