title: Mannan-modified adenovirus encoding VEGFR-2 as a vaccine to induce anti-tumor immunity.
abstract: OBJECTIVE
  Dendritic cell (DC) vaccines are a promising immunotherapeutic approach for treatment and prevention of cancer. While this methodology is widely accepted, it also has some limitations. Antigen-presenting cells including DCs express the mannan receptor (MR). The delivery of a mannan-modified tumor antigen to the MR has been demonstrated to be efficient. Vascular endothelial growth factor receptor-2 (VEGFR-2) is mainly responsible for angiogenesis and tumor growth. The goal of our study was to deliver VEGFR-2 to DCs by means of mannan-modified adenovirus.
  
  
  METHODS
  VEGFR-2 recombinant adenovirus modified with oxidized mannan was constructed as a tumor vaccine to immunize mice in vivo. IFN-γ in mouse sera and spleen was detected by ELISA and ELISPOT. The killing activity of cytotoxic T lymphocyte (CTL) against VEGFR-2 was measured with a lactate dehydrogenase assay. Vessel densities in tumor tissues were detected by immunohistochemistry. Flow cytometry was used to test CD4(+) and CD8(+) T-cell counts in tumor tissues.
  
  
  RESULTS
  The vaccine exhibited both protective and therapeutic efficacy in the inhibition of tumor growth and markedly prolonged survival in mice. Protection against metastasis was also observed. Furthermore, vaccination led to greater IFN-γ and VEGFR-2-specific CTLs. The specific immunity resulted in the suppression of angiogenesis and an increase in CD8(+) cells in tumor tissues.
  
  
  CONCLUSIONS
  Oxidized mannan-modified adenovirus expressing VEGFR-2 could extraordinarily stimulate both protective and therapeutic immune response in a mice model. Our data suggest that the combination of cancer immunity and anti-angiogenesis via modified mannan is a promising strategy in tumor prophylaxis and therapy.
authors: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guo-Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
authors: Jie
authors: J
authors: Zhang
authors: Ying
authors: Y
authors: Wang
authors: Yang
authors: Y
authors: Wu
authors: Zhen-Yu
authors: ZY
authors: Ding
authors: Xin-Mei
authors: XM
authors: Luo
authors: Wu-Ning
authors: WN
authors: Zhong
authors: Jie
authors: J
authors: Liu
authors: Xiang-Yu
authors: XY
authors: Xia
authors: Guo-Hua
authors: GH
authors: Deng
authors: Yao-Tiao
authors: YT
authors: Deng
authors: Yu-Quan
authors: YQ
authors: Wei
authors: Yu
authors: Y
authors: Jiang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D003713:Dendritic Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008351:Mannans / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D011975:Receptors, Mitogen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic; D014612:Vaccines; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D008351:Mannans; D011975:Receptors, Mitogen; D014612:Vaccines; C037935:mannan receptor; D007371:Interferon-gamma; D040301:Vascular Endothelial Growth Factor Receptor-2