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DNA vaccination against neu reduces breast cancer incidence and metastasis in mice

Cancer Gene Therapy volume 8, pages 259–268 (2001)Cite this article

Abstract

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-γ 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. Cancer Gene Therapy (2001) 8, 259–268

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Acknowledgements

We thank Walter Pagel, Department of Scientific Publications, for careful review of this manuscript and Craig A. Mullen, Department of Pediatrics, for assistance with the CTL cultures. This research was supported by the US Army Medical Research and Material Command, Department of Defense Breast Cancer Research Program, BC980071 and the W. M. Keck Center for Cancer Gene Therapy; The Breast Cancer Research Program; The Kleberg Fund for New and Innovative Research; and the Physicians Referral Service of The University of Texas M. D. Anderson Cancer Center and CA16672 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas

    Lawrence B Lachman, Xiao-Mei Rao, Ronald H Kremer & Bulent Ozpolat

  2. Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas

    Galina Kiriakova & Janet E Price

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  1. Lawrence B Lachman
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  2. Xiao-Mei Rao
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  5. Galina Kiriakova
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Correspondence to Lawrence B Lachman.

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Lachman, L., Rao, XM., Kremer, R. et al. DNA vaccination against neu reduces breast cancer incidence and metastasis in mice. Cancer Gene Ther 8, 259–268 (2001). https://doi.org/10.1038/sj.cgt.7700300

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