Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 60, Issue 6, Pages 883-893Publisher
SPRINGER
DOI: 10.1007/s00262-011-0997-3
Keywords
DNA vaccine; MTDH/AEG-1; Breast cancer; Lung metastasis; Chemosensitivity; Combination
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Funding
- Innotek Biopharmaceutical Co. Ltd.
- Shanghai Advanced Research Institute (SARI), Chinese Academy of Sciences (CAS) [1105021000]
- Nature Science Foundation of Fujian, China [2010J01372]
- National Nature Science Foundation of China [30671938, 81001177]
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The gene MTDH/AEG-1 is overexpressed in more than 40% of breast cancer patients, and it is associated with poor clinical outcomes. Previous studies have indicated that MTDH/AEG-1 could promote metastatic lung-seeding and enhance chemoresistance. Therefore, MTDH/AEG-1 could be a candidate target against breast cancer lung metastasis. We demonstrated that MTDH/AEG-1-based DNA vaccine, delivered by attenuated Salmonella typhimurium, could evoke strong CD8(+) cytotoxic-T-cell mediated immune responses against breast cancer. This vaccine showed anti-tumor growth and metastasis efficacy in a prophylactic setting. Importantly, in a therapeutic model, MTDH/AEG-1 vaccine was proved to increase chemosensitivity to doxorubicin and inhibit breast cancer lung metastasis. This vaccine could also prolong the life span of tumor-bearing mice without significant side effects in vivo. These results suggested that this novel DNA vaccine was effective in the inhibition of breast cancer growth and metastasis, and this vaccine in combination with chemotherapies offered new strategies for the clinical therapeutics of breast cancer metastasis.
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