Her-2/neu DNA vaccine controls refractory Her-2-positive breast cancer in mice

NEW YORK (Reuters Health) - Scientists in Michigan have developed a Her-2/neu DNA vaccine that causes rejection of malignant breast tumor cells implanted in mice. According to their report in the September 15 issue of Cancer Research, the vaccine induces a cytotoxic T cell response that is effective even against tumors that are resistant to current Her-2-targeted therapies.

Her-2-positive tumors often become resistant to treatment with the anti-Her-2 monoclonal antibody trastuzumab and to the tyrosine kinase inhibitors lapatinib and gefitinib, the research team at Wayne State University in Detroit explains.

Dr. Wei-Zen Wei and colleagues developed the vaccine pneuTM, which encodes the extracellular and transmembrane domains of neu. Mice vaccinated twice with pneuTM developed neutralizing anti-neu antibody as well as a T-cell response.

Immunized mice were inoculated subcutaneously with one of four neu-expressing breast cancer cell lines. Two strains are highly sensitive to both anti-neu antibody and tyrosine kinase inhibition; one strain represents treatment-induced drug-resistant cells; and one is refractory to treatment without prior selection.

In the immunized mice, "both drug-sensitive and drug-resistant tumor cells were rejected," the authors report.

In mice depleted of T cells, the vaccine failed to eradicate some drug-refractory tumors, "indicating their resistance to anti-neu antibodies," and suggesting that T-cell immunity is "indispensable for controlling drug-resistant tumors."

The investigators note that the immunized mice showed no abnormalities during the following year, a testament to the vaccine's safety.

"This (vaccine) may be an answer for women with these tumors who become resistant to the current therapies," Dr. Wei said in a press release.

"The greatest power of vaccination is protection against initial cancer development," she added, "and that is our ultimate goal with this treatment."

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