Dendritic Cells Loaded with Treating Myeloma Cells with Combination of JSI-124 and Bortezomib Can Generate Potent Myeloma-Specific CTLs Through Recovering Dysfunction of Dendritic Cells in Myeloma Patients

Abstract 4926

Signal transducers and activators of transcription 3 (STAT3) is highly activated in multiple myeloma triggered by IL-6. Although DC vaccine can induce antitumor immune response, DCs are faced with dysfunction after loading of tumor antigen. Here we show that the dysfunction of DCs from antigen loading can be recovered by treating JSI-124 and bortezomib on myeloma cells. Treatment of combination JSI-124 and bortezomib induced high expression of heat shock protein 90 (Hsp90) on the surface of dying myeloma cells, DCs loaded these myeloma cells showed low expression of p-STAT3 and reduced IL-10, IL-6 and IL-23 production without any effect on IL-12p70. Also DCs loaded with dying myeloma cells treated by JSI-124 and bortezomib combination could generate the most potent myeloma-specific CTLs targeting to myeloma cells. Our data suggested that treatment of myeloma cells with combination JSI-124 and bortezomib can recover the dying myeloma cells-loaded DC dysfunction through the highly expressed Hsp90 on tumor cells, down-regulated p-STAT3 and inhibitory cytokines, and these DCs can generate to potent myeloma-specific CTLs for obtaining better immunotherapeutic method in multiple myeloma.