Breast cancer vaccine could protect against aggressive HER2-positive breast tumours

Sep 16 2008

Women with a certain type of breast cancer have been given hope in the form of a vaccine which promises to eliminate the cancer tumours.

Researchers in the U.S. have tested the breast cancer vaccine on mice with HER2-positive tumors and they say the tumours disappeared and it even worked on cancers resistant to current anti-HER2 therapy with the added advantage that there was no toxicity.

The team from Wayne State University suggest that the vaccine could treat women with HER2-positive, treatment-resistant cancer or help prevent the cancer recurring -they also say it might potentially be used in cancer-free women to prevent the development of such cancers.

The researchers say HER2 receptors promote normal cell growth, and are found in low amounts in normal breast cells, but they can also contain many more receptors than is typical, thereby promoting a particularly aggressive type of tumour that affects up to 30% of all breast cancer patients.

Therapies such as trastuzumab and lapatinib are designed to latch on to these receptors and destroy them, but a significant number of patients develop a resistance to the drugs or the cancer metastasises and becomes more difficult to treat.

Lead investigator, Dr. Wei-Zen Wei, a professor of immunology and microbiology at the Karmanos Cancer Institute, says this treatment relies on activated, own-immunity to wipe out the cancer.

Dr. Wei says the powerful immune response against HER2-positive receptors seen in the study works even in tumours that are resistant to current therapies and the vaccine possibly has the potential to eliminate the need to even use the therapies.

The researchers say the vaccine consists of "naked" DNA - genes that produce the HER2 receptor - as well as an immune stimulant, both housed within an inert bacterial plasmid.

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.

Dr. Wei says 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 and during that process, the immune system learns to attack cancer cells that display large numbers of these receptors.

The team also used an agent that, for a while, suppressed the activity of regulatory T cells, which normally keeps the immune system from over-reacting and they say the absence of the regulatory T cells, prompted the immune system to respond much more strongly to the vaccine - when the researchers implanted HER2-positive breast tumours in the animals, the cancer was eradicated.

Dr. Wei says both tumour cells that respond to current targeted therapies and those that are resistant to these treatments were eradicated and this could provide a solution for women with these tumors who become resistant to the current therapies.

Dr. Wei's team is the first to develop HER2 DNA vaccines, and this is the second such vaccine - which they have tested more extensively.

The first was 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.

Dr. Wei says to ensure complete safety, the current test vaccine uses HER2 genes that are altered so that they cannot be oncogenic and 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 and she is certain with this vaccine, that the receptor is functionally dead.

Dr. Wei says the ultimate goal with this vaccination is to provide protection against initial cancer development.

Experts are cautious and warn that the vaccine is at a very early stage, and say it is not known if it would work in humans.

The study is published in the current issue of Cancer Research, a journal of the American Association for Cancer Research.