title: Immunity against tumor angiogenesis induced by a fusion vaccine with murine beta-defensin 2 and mFlk-1.
abstract: OBJECTIVE
  Previous studies indicated that humoral or cellular immunity against murine vascular endothelial growth factor 2 (mFlk-1) was elicited to inhibit tumor growth. Here we describe a genetic fusion vaccine, pMBD2-mFlk-1, based on the targeting of a modified mFlk-1 to antigen-presenting cells by a murine beta-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells.
  
  
  METHODS
  The protective and therapeutic antitumor immunity of the fusion vaccine was investigated in mouse models. Antiangiogenesis effect was detected by immunohistochemical staining and alginate-encapsulate tumor cell assay. The mechanisms of the fusion vaccine were primarily explored by detection of autoantibodies and CTL activity and confirmed by the deletion of immune cell subsets.
  
  
  RESULTS
  The fusion vaccine elicited a strong protective and therapeutic antitumor immunity through antiangiogenesis in mouse models, and this worked through stimulation of an antigen-specific CD8+ T-cell response as well as a specific B-cell response against mFlk-1. The findings were confirmed by depletion of immune cell subsets and in knockout mice.
  
  
  CONCLUSIONS
  Our study showed that a fusion vaccine based on self immune peptide (MBD2) and self antigen (mFlk-1) induced autoimmunity against endothelial cells, resulting in inhibition of tumor growth, and could be further exploited in clinical applications of cancer immunotherapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Guo Xue Xiang No. 37, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yong-sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Wang
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Wen
authors.forename: Lian
authors.initials: L
authors.lastname: Wang
authors.forename: Xian-cheng
authors.initials: XC
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Kan
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.forename: Canhua
authors.initials: C
authors.lastname: Huang
authors.forename: You
authors.initials: Y
authors.lastname: Lu
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Ling-yu
authors.initials: LY
authors.lastname: Fan
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.forename: Hong-bo
authors.initials: HB
authors.lastname: Wu
authors.forename: Yu-quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000517:prevention & control*; D010455:Peptides / Q000235:genetics / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D019496:Cancer Vaccines; C117047:Defb2 protein, mouse; D010455:Peptides; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D023083:beta-Defensins; C526111:pMBD2-mFlk-1 vaccine; D040301:Vascular Endothelial Growth Factor Receptor-2