TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model.
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.
Inoue
Hiroyuki
H
Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Iga
Mutsunori
M
Xin
Meng
M
Asahi
Saori
S
Nakamura
Takafumi
T
Kurita
Ryo
R
Nakayama
Masaharu
M
Nakazaki
Yukoh
Y
Takayama
Koichi
K
Nakanishi
Yoichi
Y
Tani
Kenzaburo
K
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
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