HER2 Breast Cancer Vaccine Shows Promise In Lab

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Main Category: Breast Cancer
Also Included In: Immune System / Vaccines;  Cancer / Oncology
Article Date: 15 Sep 2008 - 2:00 PDT

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Researchers in the US are hoping that their new breast cancer vaccine will be effective in humans because it safely destroyed HER2-positive tumors, even those resistant to anti-HER2 drugs, when tested on mice.

The study was the work of scientists at the School of Medicine and Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, and is published in the September 15 issue of Cancer Research, a journal of the American Association for Cancer Research.

HER2 (Human Epidermal growth factor Receptor 2) is a receptor that sits on the surface of cells in breast tissue. Their normal job is to promote cell growth, but when there are too many of them, the growth becomes uncontrolled and forms very aggressive tumors. Up to 30 per cent of breast cancers are of this HER2-positive type.

Conventional treatments rely on drugs like Herceptin (trastuzumab) and Tykerb (lapatinib) that bind to and disable the HER2 receptors, but a significant number of patients eventually become resistant to them.

The researchers hope this study will lead to a vaccine for women with HER2-positive breast cancer that has become resistant to treatment, or perhaps stop it recurring. They said it also shows promise as a cancer-prevention vaccine in women who are cancer free.

Principal investigator Dr Wei-Zen Wei, professor of immunology and microbiology at the Karmanos Cancer Institute, said the vaccine activated the patient's own immune system to destroy the cancer.

"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," said Wei.

"The vaccine could potentially eliminate the need to even use these therapies," she added.

When there is a low level of HER2, such as that expressed when they are on the surface of normal cells, the immune system ignores them. But if there is a sudden and enormous change in HER2 receptors, the immune system responds as if to an attack and learns very quickly to destroy them.

This was the mechanism that Wei and colleagues decided to provoke, using "naked" DNA genes to produce the HER2 receptors, and a stimulant to boost the immune system response. They used a bacterial plasmid to encapsulate these two ingredients and then with the aid of electrical pulses they injected them into the leg muscles of mice.

The stimulant the researchers injected at the same time as the HER2 gene, was an agent that temporarily suppresses the regulatory T cells that stop the immune system from over-reacting, thus causing a much stronger reaction than normal and giving the immunisation process a head start.

The gene very quickly produced large numbers of HER2 receptors and the immune system responded with large numbers of antibodies and killer T cells. When they implanted HER2-positive breast tumors in the animals, the cancer was eradicated. As Wei explained:

"Both tumor cells that respond to current targeted therapies and those that are resistant to these treatments were eradicated."

"This may be an answer for women with these tumors who become resistant to the current therapies," she added.

This is the second HER2 DNA vaccine that Wei and her team have developed. The first was in 1999, when they published a study that led to the development of a vaccine that is currently in early phase clinical trials in the US and Europe on women with HER2-positive breast cancer.

The new version uses HER2 genes that have been altered so they can't become "oncogenic". The earlier version retained traces of the underlying receptor structure, and when this happens there is a slight risk this can trigger tumor formation later, because the "signalling" system of the receptor is still active and can communicate with the cell nucleus.

Wei said the first vaccine was safe, but it contained a bit more of the "native" HER2 receptor structure, whereas "With this vaccine, I am quite certain the receptor is functionally dead," she said.

Wei said that their ultimated goal was to protect against cancer developing in the first place, which is "the greatest power of vaccination".

"DNA Vaccination Controls Her-2+ Tumors that Are Refractory to Targeted Therapies."
Paula J. Whittington, Marie P. Piechocki, Henry H. Heng, Jennifer B. Jacob, Richard F. Jones, Jessica B. Back, and Wei-Zen Wei
Cancer Res 68, 7502-7511, September 15, 2008.
doi: 10.1158/0008-5472.CAN-08-1489

Click here for Abstract.

Source: Journal abstract, American Association for Cancer Research.

Written by: Catharine Paddock, PhD


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