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Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2

Cancer Gene Therapy volume 14, pages 158–164 (2007)Cite this article

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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Authors and Affiliations

  1. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, The People's Republic of China

    T Yi, Y-Q Wei, L Tian, J Li, H-X Deng, Y-J Wen, C-H Zou, G-H Tan, B Kan, J-M Su, Y Jiang, Y-Q Mao, P Chen & Y-S Wang

  2. Department of Gynecology and Obstetrics, Second West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, The People's Republic of China

    T Yi & X Zhao

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  1. T Yi
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Correspondence to Y-Q Wei.

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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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