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

Author: Sypniewska Roza  

Publisher: Springer Publishing Company

ISSN: 0167-6806

Source: Breast Cancer Research and Treatment, Vol.91, Iss.1, 2005-05, pp. : 19-28

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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</i>, the mouse homologue of the human Mage-b1/2</i>. 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-b</i>transcripts 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</i> 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-</i>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</i> 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</i>=0.0329; vaccine versus saline, p</i>=0.0128). The observed protective efficacy of the Mage-b</i> DNA vaccine correlated with high levels of vaccine-induced IFN in spleen and lymph nodes upon re-stimulation in vitro</i>. These results demonstrate the potential of TAA-based DNA vaccines in controlling metastatic disease in breast cancer patients.