Sequential actions of immune effector cells induced by viral activation of dendritic cells to eliminate murine neuroblastoma.

PURPOSE: In preclinical trails, we reported the antitumor effect of dendritic cells activated with Sendai virus (rSeV/DC) combined with γ-irradiation against neuroblastoma. However, what kind of effector cells for the combined therapy were used to show the antitumor effect was unclear. In this study, we performed radiation and rSeV/DC therapy in vivo and examined the effector cells involved. METHODS: Dendritic cells were cultured from bone marrow cells, activated with SeV and administered intratumorally at 106 weekly for 3weeks. Radiation was administered at 4Gy/time × 3 times. During the treatment, CD4+ and CD8+ cells and natural killer (NK) cells were removed by antibodies. RESULTS: Complete remission of neuroblastoma was observed in 62.5% of individuals in the combined therapy group. By depleting the effector cells using antibodies, the tumor increased in size from an early stage of treatment in the CD4+ and NK cell-depleted group. In contrast, the tumor increased in size in the late stage of treatment in the CD8+ cell-depleted group. CONCLUSION: The combination of radiation and rSeV/DC therapy induces different effector cells, depending on the time point during treatment. LEVEL OF EVIDENCE: V.