Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis.
BACKGROUND
Overexpression of the HER2/neu gene in breast cancer is associated with an increased incidence of metastatic disease and with a poor prognosis. Although passive immunotherapy with the humanized monoclonal antibody trastuzumab (Herceptin) has shown some effect, a vaccine capable of inducing T-cell and humoral immunity could be more effective.


METHODS
Virus-like replicon particles (VRP) of Venezuelan equine encephalitis virus containing the gene for HER2/neu (VRP-neu) were tested by an active immunotherapeutic approach in tumor prevention models and in a metastasis prevention model.


RESULTS
VRP-neu prevented or significantly inhibited the growth of HER2/neu-expressing murine breast cancer cells injected either into mammary tissue or intravenously. Vaccination with VRP-neu completely prevented tumor formation in and death of MMTV-c-neu transgenic mice, and resulted in high levels of neu-specific CD8+ T lymphocytes and serum IgG.


CONCLUSIONS
On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu+ breast cancer is warranted.
Wang
Xiaoyan
X
Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. xywang@mdanderson
Wang
Jian-Ping
JP
Maughan
Maureen F
MF
Lachman
Lawrence B
LB
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology*; D002471:Cell Transformation, Neoplastic; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics; D005260:Female; D018734:Genes, erbB-2; D015316:Genetic Therapy; D005822:Genetic Vectors; D007167:Immunotherapy / Q000379:methods; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D012093:Replicon; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines