Research article

Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis

Xiaoyan Wang^1,2, Jian-Ping Wang¹, Maureen F Maughan³ and Lawrence B Lachman^1,2*

• * Corresponding author: Lawrence B Lachman Lachman@odin.mdacc.tmc.edu

Author Affiliations

¹ Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

² The Graduate School of Biomedical Sciences, The University of Texas Health Sciences Center, Houston, Texas, USA

³ AlphaVax, Inc., Research Triangle Park, North Carolina, USA

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Breast Cancer Res 2005, 7:R145-R155 doi:10.1186/bcr962

Published: 29 November 2004

Abstract

Introduction

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.

Conclusion

On the basis of these findings, clinical testing of this vaccine in patients with HER2/neu⁺ breast cancer is warranted.