698. IL-23 Transduced Dendritic Cells Produce a Potent Tumor-Specific Immunity Against Intracranial Gliomas

Abstract

Top of pageAbstract L-23 is a recently discovered cytokine consisting of a heterodimer of the IL-12 p40 subunit and a novel 19-kDa protein, termed p19. IL-23 preferentially induces proliferation of, and IFN-|[gamma]| production by, memory T cells. In the present study, we transduced freshly cultured dendritic cells (DC) with an adenoviral vector carrying the single-chain IL-23 cDNA. Message RNA and protein expression of IL-23 from the transduced DC were detected by RT-PCR and ELISA respectively. Intratumoral implanting IL-23 expressing DC into intracranial GL-26 glioma bearing C57bl/6 mice resulted in prolonged survival compared with the control mice, which were intracranial bearing GL-26 glioma implanted with empty vector transduced DC. Enhanced CD8+ T cells infiltration within the tumors were detected by immunohistochemistry in brain sections from the mice treated by IL-23 expression DC. Cytotoxic T lymphocyte (CTL) assay of the spleen cells from the IL-23 expressing DC treated mice shown that CTL activities against GL-26 glioma but not irrelevant tumors were augmented. In addition, the mice survived intracranial glioma by IL-23 expressing DC treatment were resistant to intracranial rechallenge with the same GL-26 cell line. This tumor-specific protective immunity was associated with enhanced IFN-|[gamma]| expression in the brain. Furthermore, the antitumor activities of IL-23 expressing DC was also observed in athymic nude mice but greatly impaired compared with that in C57bl/6 mice. Natural killer cells depletion for the athymic nude mice abolished the antitumor function. Taken together, these data suggest that DC as powerful antigen presenting cells can elicit tumor-specific antitumor immune responses after transduced by IL-23. T cells are crucial for the antitumor activity of the IL-23 expressing DC and natural killer cells are also involved in the process.