title: B7-H1 protein vaccine induces protective and therapeutic antitumor responses in SP2/0 myeloma-bearing mice.
abstract: B7-H1 is a co-inhibitory molecule belonging to the B7 family. The B7-H1 protein is only expressed on macrophage lineage of cells in normal tissues, but is overexpressed in most types of tumor. The aberrant expression of cell surface B7-H1 on cancer cells is generally associated with high-risk prognostic factors. The tumor-associated B7-H1 increases apoptosis of antigen-specific T cells through interaction with its receptor PD-1 on CD8+ T cells and contributes to tumor immune evasion. These features suggest that B7-H1 may be a therapeutic target for the B7-H1-expressing tumors. We developed a therapeutic vaccine by coupling a tetanus toxoid T-helper cell epitope with the N-terminal of B7-H1 IgV-like domain. This vaccine was able to induce high titers of antibodies against B7-H1 in mice which were able to bind to native cell surface B7-H1. We chose the B7-H1-expressing SP2/0 myeloma and its syngeneic host (the BALB/c mouse) as the model to study the antitumor activity of the rhB7-H1M vaccine. Vaccination with this modified B7-H1 protein resulted in almost complete protection from SP2/0 tumor challenge and efficiently eliminated pre-established tumors in mice. In addition, B7-H1 vaccination was able to decrease the percentage of CD4+ Foxp3+ regulatory T cells in tumor-bearing mice and which might improve antitumor immunity. These data demonstrate the potential of B7-H1-based vaccine as a therapeutic agent for the treatment of cancer overexpressing B7-H1.
authors: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Cun
authors: C
authors: Zhang
authors: Weihua
authors: W
authors: Wang
authors: Xin
authors: X
authors: Qin
authors: Yujin
authors: Y
authors: Xu
authors: Tonglie
authors: T
authors: Huang
authors: Qiang
authors: Q
authors: Hao
authors: Weina
authors: W
authors: Li
authors: Shouzhen
authors: S
authors: Wu
authors: Yingqi
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D000906:Antibodies; D060890:B7-H1 Antigen; D019496:Cancer Vaccines