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

Abstract

PurposeIn 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. MethodsDendritic 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. ResultsComplete 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. ConclusionThe combination of radiation and rSeV/DC therapy induces different effector cells, depending on the time point during treatment. Level of EvidenceV.