1. Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2
- Author
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Yan-jun Wen, Guang-hong Tan, Chun-hua Zou, Yu Jiang, Ling Tian, Xinyu Zhao, Jin-Hua Su, Tao Yi, Yun Qiu Mao, Jiyao Li, Yu Quan Wei, Bing Kan, Yueqi Wang, Ping Chen, and Hong Xin Deng
- Subjects
Cancer Research ,Cellular immunity ,Adoptive cell transfer ,DNA, Complementary ,medicine.medical_treatment ,Blotting, Western ,Biology ,Cancer Vaccines ,Immune tolerance ,DNA vaccination ,Mice ,Cancer immunotherapy ,T-Lymphocyte Subsets ,Cell Line, Tumor ,Vaccines, DNA ,medicine ,Animals ,Cytotoxic T cell ,Molecular Biology ,Autoantibodies ,DNA Primers ,Immunity, Cellular ,Mice, Inbred BALB C ,Base Sequence ,Neovascularization, Pathologic ,Reverse Transcriptase Polymerase Chain Reaction ,Cancer ,medicine.disease ,Immunohistochemistry ,Mice, Inbred C57BL ,Antibody Formation ,Colonic Neoplasms ,Immunology ,Matrix Metalloproteinase 2 ,Molecular Medicine ,Chickens ,CD8 - 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.
- Published
- 2006