DNA vaccination against neu reduces breast cancer incidence and metastasisin mice

The gene for HER2/neu is overexpressed in 30-40% of breast and ovarian canc ers, 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 f or vaccination. We inserted the sequence for neu into a novel plasmid calle d ELVIS containing a Sindbis virus replicon that reproduces multiple copies of mRNA. Mice vaccinated one time intramuscularly demonstrated a strong an tibody 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 challen ged with tumor cells lacking the neu insert. Intradermal vaccination was al so protective and required 80% less plasmid for a similar level of protecti on. Vaccination reduced the incidence of lung metastasis from mammary fatpa d tumors and reduced the number of lung metastases resulting from intraveno us injection of A2L2 cells. Cytotoxic T lymphocytes cultures of immune sple en cells with P815-neu cells produced high levels of interferon-gamma indic ating an antigen-specific Th1-type immune response resulting from the vacci nation. In a spontaneous breast tumor model using neu transgenic mice, vacc ination with ELVIS-neu protected against development of spontaneous breast tumors. Our preclinical data indicate that therapeutic vaccination of patie nts with ELVIS-neu may reduce metastasis from HER2/neu-expressing breast an d ovarian tumors.