MP28-01 GENERATION OF POTENT CYTOTOXIC T LYMPHOCYTES AGAINST BLADDER CANCER CELLS BY DENDRITIC CELLS LOADED WITH DYING T24 BLADDER CANCER CELLS

Abstract

INTRODUCTION AND OBJECTIVES: To induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy against bladder cancer, various tumor antigens need to be loaded onto DCs. The aim of this study was to establish a method of immunotherapy for bladder cancer using bladder cancer-specific CTLs generated in vitro by DCs. METHODS: Monocyte-derived DCs from bladder cancer patients were induced to mature in a standard cytokine cocktail (in IL-1b, TNF-a, IL-6, and PGE2: standard DCs, sDCs) or in an a-type 1-polarized DC (aDC1) cocktail (in IL-1b, TNF-a, IFN-b, IFN-g, and polyinosinic:polycytidylic acid) and then loaded with the UVB-irradiated bladder cancer cell line T24. Antigen-loaded aDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay. RESULTS: The aDC1s significantly increased the expression of several molecules related to DC maturation, regardless of whether the aDC1s were loaded with tumor antigens or not, compared to sDCs. The aDC1sshowedahigherproductionof interleukin-12bothduringmaturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens as compared to standard DCs (sDCs). Bladder cancer-specific CTLs against autologous bladder cancer cells were successfully induced by aDC1s loaded with dying T24 cells. CONCLUSIONS: Autologous aDC1s loaded with an allogeneic bladder cancer cell line can generate greater bladder cancer-specific CTL responses and may provide a novel source of DC-based vaccines that can be used for the development of immunotherapy in patients with bladder cancer.