The gene for HER2/neu is overexpressed in 30-40% of breast and
ovarian cancers, and this overexpression correlates with increased
metastasis and poor prognosis. The HER2/neu gene product, a transmembrane
protein kinase member of the
EGF receptor family, has significant potential as a
tumor antigen for vaccination. We inserted the sequence for neu into a novel plasmid called
ELVIS containing a Sindbis virus replicon that reproduces multiple copies of
mRNA. Mice vaccinated one time intramuscularly demonstrated a strong antibody response against A2L2, a murine
breast cancer cell line transfected to express neu. Vaccinated mice challenged in the mammary fatpad with A2L2 had reduced
tumor incidence and reduced
tumor mass compared to mice challenged with
tumor cells lacking the neu insert. Intradermal vaccination was also protective and required 80% less plasmid for a similar level of protection. Vaccination reduced the incidence of lung
metastasis from mammary fatpad
tumors and reduced the number of lung
metastases resulting from
intravenous injection of A2L2 cells. Cytotoxic T lymphocytes cultures of immune spleen cells with P815-neu cells produced high levels of
interferon-gamma indicating an
antigen-specific Th1-type immune response resulting from the vaccination. In a spontaneous
breast tumor model using neu transgenic mice, vaccination with
ELVIS-neu protected against development of spontaneous
breast tumors. Our preclinical data indicate that therapeutic vaccination of patients with
ELVIS-neu may reduce
metastasis from HER2/neu-expressing breast and ovarian
tumors.