24-10-2012, 05:50 PM
The Use of Venezuelan Equine Encephalitis Replicons Encoding the HER-2/neu Tumor Associated Antigen for the Prevention and Treatment of Breast Cancer
ABSTRACT
Overexpression and amplification of the Her-2/neu proto-oncogene has been implicated in the development of aggressive
human breast cancer. Consequently, Her-2/neu provides a potential target for immunotherapy. Indeed, Her-2/neu specific
cytotoxic T lymphocytes (CTL) can be detected in patients with breast and ovarian cancer. Nevertheless, the observed
response to Her-2/neu is inadequate to prevent tumor progression. Our overall goal is to determine whether genetic vaccination
is a feasible strategy to enhance Her-2/neu specific T cell activity, and in turn prevent and/or treat breast cancer. Using
Venezuelan Equine Encephalitis virus replicons encoding Her-2/neu we have’ been able to generate neu specific cytotoxicity
in vaccinated mice. Further, we have demonstrated in vivo efficacy in mice challenged with neu expressing tumor cells, and
have noted a delay in the onset of spontaneous adenocarcinoma in vaccinated’ neu transgenic mice.