Immunogene therapy of tumors with a vaccine based on the ligand-binding domain of chicken homologous integrin beta3.
The breaking of immune tolerance against angiogenesis-associated molecules should be a useful approach for cancer therapy by active immunity. We used chicken integrin beta3 as a model antigen to explore the feasibility of immunogene therapy of the tumors with a vaccine based on a single xenogeneic homologous gene, targeting the molecules associated with angiogenesis. To test this concept we constructed a plasmid DNA encoding the ligand-binding domain of chicken integrin beta3 (P-BD-C) and control vectors. We found that immunogene therapy of tumors with a vaccine based on the ligand-binding domain of chicken integrin beta3 (P-BD-C) was effective in both protective and therapeutic anti-tumor immunity in several tumor models in mice. Autoantibodies against integrin beta3 in sera of mice immunized with the ligand-binding domain of chicken integrin beta3 could be found by Western blot analysis and ELISA assay. The purified immunoglobulins were effective in the inhibition of endothelial cell proliferation in vitro, and in anti-tumor activity as well as in the inhibition of angiogenesis by adoptive transfer in vivo. The anti-tumor activity and the production of integrin beta3-specific autoantibodies (manifested by significantly elevated Ig G1 and Ig G2b) could be abrogated by the depletion of CD4+ T lymphocytes. These observations may provide a vaccine strategy for cancer therapy through the induction of the autoimmunity against the molecules associated with tumor growth in a cross-reaction with a single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.
Lou
Yan-Yan
YY
Cancer Research Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, The People's Republic of China.
Wei
Yu-Quan
YQ
Yang
Li
L
Zhao
Xia
X
Tian
Ling
L
Lu
You
Y
Wen
Yan-Jun
YJ
Liu
Fen
F
Huang
Mei-Juan
MJ
Kang
Bin
B
Xiao
Fei
F
Su
Jing-Mei
JM
He
Qu-Ming
QM
Xie
Xing-Jiang
XJ
Mao
Yun-qiu
YQ
Lei
Song
S
Liu
Ji-Yan
JY
Lou
Fen
F
Zhou
Li-qun
LQ
Peng
Feng
F
Jiang
Yu
Y
Hu
Bing
B
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology*; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D039661:Integrin beta3 / Q000235:genetics* / Q000276:immunology; D008024:Ligands; D051379:Mice; D009389:Neovascularization, Pathologic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D001323:Autoantibodies; D019496:Cancer Vaccines; D039661:Integrin beta3; D008024:Ligands; D019444:Vaccines, DNA