title: TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model.
abstract: BACKGROUND
  Transduction of the granulocyte-macrophage colony stimulating factor (GM-CSF) gene into mouse tumor cells abrogates their tumorigenicity in vivo. Our previous report demonstrated that gene transduction of GM-CSF with either TARC or RANTES chemokines suppressed in vivo tumor formation. In this paper, we examined whether the addition of either recombinant TARC or RANTES proteins to irradiated GM-CSF-transduced tumor vaccine cells enhanced antitumor immunity against established mouse tumor models to examine its future clinical application.
  
  
  METHODS
  Three million irradiated WEHI3B cells retrovirally transduced with murine GM-CSF cDNA in combination with either recombinant TARC or RANTES were subcutaneously inoculated into syngeneic WEHI3B-preestablished BALB/c mice.
  
  
  RESULTS
  Vaccinations were well tolerated. Mice treated with GM-CSF-transduced cells and the chemokines demonstrated significantly longer survival than mice treated with GM-CSF-transduced cells alone. Splenocytes harvested from mice treated with the former vaccines produced higher levels of IL-4, IL-6, IFN-gamma, and TNF-alpha, suggesting enhanced innate and adaptive immunity. Immunohistochemical analysis of tumor sections after vaccination revealed a more significant contribution of CD4+ and CD8+ T cells to tumor repression in the combined vaccine groups than controls.
  
  
  CONCLUSIONS
  TARC and RANTES enhance the immunological antitumor effect induced by GM-CSF in mouse WEHI3B tumor models and may be clinically useful.
authors.affiliation: Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Iga
authors.forename: Meng
authors.initials: M
authors.lastname: Xin
authors.forename: Saori
authors.initials: S
authors.lastname: Asahi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ryo
authors.initials: R
authors.lastname: Kurita
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakayama
authors.forename: Yukoh
authors.initials: Y
authors.lastname: Nakazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani
mesh_terms: D000818:Animals; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D054414:Chemokine CCL17 / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology*; D013154:Spleen / Q000166:cytology
chemical_list: D019496:Cancer Vaccines; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D018946:Chemokine CCL5; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor