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Interleukin 18 Transfection Enhances Antitumor Immunity Induced by Dendritic Cell-Tumor Cell Conjugates¹

Department of Immunology, Second Military Medical University, Shanghai 200433, People’s Republic of China [D.W.J., Q.T., G.L., M.B., L.H., X.C.], and Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892 [Y.Y.]

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-. 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-.

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