Prevention of metastases with a Mage-b DNA vaccine in a mouse breast tumor model: Potential for breast cancer therapy

Roza K. Sypniewska, Lieve Hoflack, Melissa Tarango, Susan Gauntt, Belinda Z. Leal, Robert L. Reddick, Claudia Gravekamp

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Anti-tumor vaccines are a relatively non-toxic alternative to conventional chemotherapeutic strategies to control breast cancer. Immunization with tumor-associated antigens (TAAs) triggers anti-tumor cytotoxic T lymphocytes (CTL), which can limit tumor progression. Here we report on the development and effectiveness of a TAA-based DNA vaccine encoding Mage-b1/2, the mouse homologue of the human MAGE-B1/2. As model system, we used immune competent Balb/c mice with syngeneic non-metastatic (64pT) or metastatic (4TO7cg) breast tumors. First, the presence of Mage-btranscripts in the 64pT and 4TO7cg breast tumors and metastases was demonstrated by RT-PCR, Southern blotting, and DNA sequencing. A DNA-based vaccine was developed from transcripts of one of the 64pT tumors, encoding the complete Mage-b1/2 protein, and subsequently tested for its preventive efficacy in both breast tumor models. Mice were immunized two times intramuscularly with the vaccine (pcDNA3.1-Mage-b1/2-V5), the control vector (pcDNA3.1-V5), or saline. Two weeks after the last immunization, the syngeneic 4TO7cg or 64pT tumor cell lines were injected in a mammary fat pad. Mice were monitored during the next 4 weeks for tumor formation, latency and size, and subsequently sacrificed for analysis. While the Mage-b1/2 vaccine had only a minor effect on the latency and growth of primary tumors, a significant and reproducible reduction in the number of 4TO7cg metastases was observed (vaccine versus control vector, p=0.0329; vaccine versus saline, p=0.0128). The observed protective efficacy of the Mage-b DNA vaccine correlated with high levels of vaccine-induced IFNγ in spleen and lymph nodes upon re-stimulation in vitro. These results demonstrate the potential of TAA-based DNA vaccines in controlling metastatic disease in breast cancer patients.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalBreast Cancer Research and Treatment
Volume91
Issue number1
DOIs
Publication statusPublished - May 1 2005
Externally publishedYes

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Keywords

  • 4TO7cg model
  • 64pT model
  • Breast tumor model
  • Mage-b DNA vaccine
  • Metastases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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