Interleukin 18 transfection enhances antitumor immunity induced by dendritic cell-tumor cell conjugates.
Dendritic cell (DC)-based tumor vaccine represents a promising approach to the immunotherapy of malignant tumors. We prepared a novel type of DC-based vaccine, stable conjugates of DCs and EL4 cells transduced with cDNA of OVA (E.G7). Immunization with DC-E.G7 conjugates led to generation of T helper (Th) 1 cytokine-producing cells, antigen-specific CD8(+) T cells, and strong antitumor immunity that is dependent on both CD4(+) T cells and CD8(+) T cells. To further increase the potency of the vaccine, interleukin 18-transfected DCs were used to prepare the IL18DC-E.G7 conjugates. Immunization with such conjugates significantly increased the production of Th1 cytokine-producing cells and the number of antigen-specific CD8(+) T cells, as well as stronger antitumor immunity. Furthermore, the increased Th1 cytokine production and stronger antitumor effect were not observed in mice depleted of IFN-gamma. These data indicated that DC-tumor cell conjugates are a potent tumor vaccine. Interleukin 18 can be administrated using gene-transfected cells and enhances antitumor immunity, which is mainly mediated by IFN-gamma.
Ju
D W
DW
Department of Immunology, Second Military Medical University, Shanghai 200433, People's Republic of China.
Tao
Q
Q
Lou
G
G
Bai
M
M
He
L
L
Yang
Y
Y
Cao
X
X
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D013945:Thymoma / Q000276:immunology / Q000473:pathology; D014162:Transfection
D019496:Cancer Vaccines; D018076:DNA, Complementary; D018984:Epitopes, T-Lymphocyte; D020382:Interleukin-18; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma