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

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Summary

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.

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Authors and Affiliations

  1. Department of Cellular and Structural Biology, University of Texas Health Science Center, STCBM building, 15355 Lambda Drive, San Antonio, TX, 78245, USA

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

  2. Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA

    Robert L. Reddick

Authors
  1. Roza K. Sypniewska
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  2. Lieve Hoflack
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  3. Melissa Tarango
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  4. Susan Gauntt
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  5. Belinda Z. Leal
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  7. Claudia Gravekamp
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Correspondence to Claudia Gravekamp.

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Sypniewska, R.K., Hoflack, L., Tarango, M. et al. Prevention of metastases with a Mage-b DNA vaccine in a mouse breast tumor model: potential for breast cancer therapy. Breast Cancer Res Treat 91, 19–28 (2005). https://doi.org/10.1007/s10549-004-6454-7

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