10052- IMT-2 TRANSRATIONAL RESEARCH FOR A MULTICENTER CLINICAL TRIAL OF TUMOR-FUSED DENDRITIC CELL IMMUNOTHERAPY

Abstract OBJECTIVE Although an immunotherapy using tumor-fused dendritic cells (TFDC) is considered promising as one of the multimodality therapies for malignant gliomas, it has not been able to perform it in hospitals without a cell processing facility because the method of transporting a raw material and preserving the final product have not been established. We performed a non-clinical study to address these challenges with the aim of conducting a multicenter investigator-initiated clinical trial. METHODS In a study for establishing a transport method of raw material, removed glioma tissue in a surgery was transported under refrigerated storage from an affiliated hospital of the Jikei University to the JIEKI-CPF that is a manufacturing base of TFDC located at a remote place. Cultured tumor cells were tried to establish using the tissues refrigerated for 24, 48, and 72 hours. In a study for establishing a cryopreserve method of TFDC, TFDC was manufactured using established cultured tumor cells and dendritic cells of the same patient, suspended in a cryoplastic solution on the day after manufacture, frozen in gas-phase liquid nitrogen for 13 weeks, and thawed to confirm its viability. An analysis of mixed lymphocyte reaction was performed to confirm the function of TFDC after thawing. RESULTS Cultured tumor cells were successfully established from the tumor tissues of all registered 4 cases (3 cases of glioblastoma, 1 case of anaplastic oligodendroglioma) at all refrigerated periods. Count and viability of TFDC cryopreserved for 13 weeks were achieved the target values. Increased secretion of IFNγ induced by TFDC was confirmed in an analysis of mixed lymphocyte reaction. CONCLUSIONS Despite the high efficacy and safety of TFDC immunotherapy, its un-versatility has limited its use to single centers. We aim to conduct an investigator-initiated multicenter clinical trial based on the data from this non-clinical study.