Abstract
Matrix metalloproteinase-2 (MMP-2) has been used as a target for cancer immunotherapy. The activation of immunization by breaking immune tolerance to self-MMP-2 may be one of the promising approaches for the treatment of MMP-2-positive tumors. In this study, we constructed the xenogeneic tumor cell vaccine c-MMP-2 by transfecting CT26 and LLC cells with chicken MMP-2 cDNA constructs. MMP-2-specific autoantibodies in sera and tumor cells were found in mice immunized with c-MMP-2. Protection against tumor growth was evaluated in respect of the relative contributions of autoantibodies, CD4+, and CD8+ T cells. Treatment with this vaccine (c-MMP-2) also prolonged the survival time of mice bearing cancer. The specific cytotoxic T-cell responses suggested that the treatment increased CD8+ T-cell activity. The antitumor activity of c-MMP-2 was abrogated by in vivo depletion of CD4+ and CD8+ T-lymphocytes and improved by adoptive transfer of CD4+ and CD8+ T-lymphocytes from the mice treated with c-MMP-2. An alternative DNA vaccination strategy for cancer therapy was identified in this study by eliciting humoral and cellular immunoresponse with a crossreacting transfectant.
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Abbreviations
- c-MMP-2:
-
tumor cells transfected with plasmid DNA encoding chicken MMP-2
- m-MMP-2:
-
tumor cells transfected with plasmid DNA encoding mouse MMP-2
- e-p:
-
tumor cells transfected with empty vector
- mAb:
-
monoclonal antibodies
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Acknowledgements
This work was supported by National Key Basic Research Program of China (2004CB518800 and 2001CB510001), Project of National Natural Sciences Foundation of China, national 863 project.
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Yi, T., Wei, YQ., Tian, L. et al. Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2. Cancer Gene Ther 14, 158–164 (2007). https://doi.org/10.1038/sj.cgt.7700994
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DOI: https://doi.org/10.1038/sj.cgt.7700994
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