title: Immunogene therapy of tumors with a vaccine based on the ligand-binding domain of chicken homologous integrin beta3.
abstract: 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.
authors: Cancer Research Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, The People's Republic of China.
authors: Yan-Yan
authors: YY
authors: Lou
authors: Yu-Quan
authors: YQ
authors: Wei
authors: Li
authors: L
authors: Yang
authors: Xia
authors: X
authors: Zhao
authors: Ling
authors: L
authors: Tian
authors: You
authors: Y
authors: Lu
authors: Yan-Jun
authors: YJ
authors: Wen
authors: Fen
authors: F
authors: Liu
authors: Mei-Juan
authors: MJ
authors: Huang
authors: Bin
authors: B
authors: Kang
authors: Fei
authors: F
authors: Xiao
authors: Jing-Mei
authors: JM
authors: Su
authors: Qu-Ming
authors: QM
authors: He
authors: Xing-Jiang
authors: XJ
authors: Xie
authors: Yun-qiu
authors: YQ
authors: Mao
authors: Song
authors: S
authors: Lei
authors: Ji-Yan
authors: JY
authors: Liu
authors: Fen
authors: F
authors: Lou
authors: Li-qun
authors: LQ
authors: Zhou
authors: Feng
authors: F
authors: Peng
authors: Yu
authors: Y
authors: Jiang
authors: Bing
authors: B
authors: Hu
mesh_terms: 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*
chemical_list: D001323:Autoantibodies; D019496:Cancer Vaccines; D039661:Integrin beta3; D008024:Ligands; D019444:Vaccines, DNA