Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2.
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.
Yi
T
T
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, The People's Republic of China.
Wei
Y-Q
YQ
Tian
L
L
Zhao
X
X
Li
J
J
Deng
H-X
HX
Wen
Y-J
YJ
Zou
C-H
CH
Tan
G-H
GH
Kan
B
B
Su
J-M
JM
Jiang
Y
Y
Mao
Y-Q
YQ
Chen
P
P
Wang
Y-S
YS
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*
D001323:Autoantibodies; D019496:Cancer Vaccines; D017931:DNA Primers; D018076:DNA, Complementary; D019444:Vaccines, DNA; D020778:Matrix Metalloproteinase 2