title: Enhancement of DNA vaccine efficacy by targeting the xenogeneic human chorionic gonadotropin, survivin and vascular endothelial growth factor receptor 2 combined tumor antigen to the major histocompatibility complex class II pathway.
abstract: BACKGROUND
  A number of strategies have been used to improve the efficacy of the DNA vaccine for the treatment of tumors. These strategies, ranging from activating CD4+ T cell, manipulating antigen presentation and/or processing to anti-angiogenesis, focus on one certain aspect in the functioning of the vaccine. Therefore, their combination is necessary for rational DNA vaccines design by synergizing different regimens and overcoming the limitations of each strategy.
  
  
  METHODS
  A DNA fragment (HSV) encoding the C terminal 37 amino acids of human chorionic gonadotropin β chain (hCGβ), 5 different HLA-restricted cytotoxic T lymphocyte epitopes from human survivin and the third and fourth extracellular domains of vascular endothelial growth factor receptor 2 (VEGFR2) was inserted into the sequence between the luminal and transmembrane domain of human lysosome-associated membrane protein-1 cDNA for the construction of a novel DNA vaccine.
  
  
  RESULTS
  This novel vaccine, named p-L/HSV, has a potent antitumor effect on the LL/2 lung carcinoma model in syngeneic C57BL/6 mice. The immunologic mechanism involved in the antitumor effect referred to the activation of both cellular and humoral immune response. In addition, the tumor vasculature was abrogated as observed by immunohistochemistry in p-L/HSV immunized mice. Furthermore, the immunized mice received an additional boost with p-L/HSV 6 months later and showed a strong immune recall response.
  
  
  CONCLUSIONS
  The present study indicates that the strategies of combining antitumor with antiangiogenesis and targeting the tumor antigen to the major histocompatibility complex class II pathway cooperate well. Such a study may shed new light on designing vaccine for cancer in the future.
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Wei
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Sun
authors.forename: Chaojun
authors.initials: C
authors.lastname: Song
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Yongming
authors.initials: Y
authors.lastname: Li
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: Jiuyu
authors.initials: J
authors.lastname: Gong
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Zhijia
authors.initials: Z
authors.lastname: Liu
authors.forename: J T
authors.initials: JT
authors.lastname: August
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000628:therapy*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage*; D057809:HEK293 Cells; D006801:Humans; D007110:Immunity, Active / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000939:Epitopes; D051034:Inhibitor of Apoptosis Proteins; D051907:Lysosomal Membrane Proteins; D000077022:Survivin; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2; C107489:BIRC5 protein, human; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1