Experimental HER2 Vaccine Protects Against Breast Cancer

Results of a pre-clinical trial in mice indicated that a vaccine against the HER/neu membrane protein eliminated HER2-positive tumors in mice - even cancers resistant to current anti-HER2 therapy - without any toxicity.

Approximately 25-30% of breast cancers have an amplification of the HER2/neu gene or overexpression of its protein product. Overexpression of this receptor in breast cancer is associated with increased disease recurrence and worse prognosis.

HER2/neu is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family. HER2/neu is notable for its role in the pathogenesis of breast cancer and as a target of treatment. It is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation. HER2 is thought to be an orphan receptor, with none of the EGF family of ligands able to activate it. However, ErbB receptors form dimers on ligand binding, and HER2 is the preferential dimerization partner of other members of the ErbB family. The HER2 gene is a proto-oncogene located at the long arm of human chromosome 17(17q11.2-q12).

Investigators at Wayne State University (Detroit, MI, USA) used pulses of electricity as the means to inject a "naked” DNA virus into the leg muscles of mice. The DNA, which coded for the HER2 receptor, was packaged together with an immune stimulant in an inert bacterial plasmid. The HER2 genes used in the experimental vaccine had been modified so that they could not be oncogenic.

Results published in the September 15, 2008, issue of the journal Cancer Research revealed that the injected gene was integrated into cells and that it manufactured a large quantity of HER2 receptors that activated both antibodies and killer T cells. The fully aroused immune system was able to eradicate both tumor cells that responded to current targeted therapies and those that were resistant to these treatments.

"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,” explained senior author Dr. Wei-Zen Wei, professor of immunology and microbiology at Wayne State University. "During that process, the immune system learns to attack cancer cells that display large numbers of these receptors. 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. The vaccine could potentially eliminate the need to even use these therapies.”

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