title: Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2.
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.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, The People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Yi
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Tian
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: H-X
authors.initials: HX
authors.lastname: Deng
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Wen
authors.forename: C-H
authors.initials: CH
authors.lastname: Zou
authors.forename: G-H
authors.initials: GH
authors.lastname: Tan
authors.forename: B
authors.initials: B
authors.lastname: Kan
authors.forename: J-M
authors.initials: JM
authors.lastname: Su
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Mao
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: Y-S
authors.initials: YS
authors.lastname: Wang
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D001483:Base Sequence; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D002645:Chickens; D003110:Colonic Neoplasms / Q000276:immunology*; D017931:DNA Primers; D018076:DNA, Complementary; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D019496:Cancer Vaccines; D017931:DNA Primers; D018076:DNA, Complementary; D019444:Vaccines, DNA; D020778:Matrix Metalloproteinase 2