C3H系マウスに骨肉腫LM８細胞株を移植し、原発巣を切除して肺転移のみとした実験系で、免疫チェックポイント阻害（PD-L1抗体 、Tim-3抗体）とOX-40抗体による免疫系賦活を同時に行う免疫療法の効果を検討した。免疫療法群で有意な生存率の改善と肺転移巣の縮小が示された。原原発巣切除により免疫療法単独もしくは原発巣切除のみの場合よりも有意に高い生存率が得られ、この新規免疫療法の有用性が示された。神経芽腫細胞株移植モデルを用いた検討では免疫療法の効果が残存腫瘍細胞数に影響されることが示された。一方でヒト小児がん組織では化学療法前後とも免疫チェックポイント蛋白ならびに関連分子の発現は弱かった。
In a pediatric metastatic cancer model using osteosarcoma cell line LM8 cells transplanted to C3H mice, efficacy of the immunotherapy by inhibiting immune check-point protein using anti-PDL1 antibody and Tim-3 antibody with simultaneous immune activation by OX-40 was verified.  The mice treated by the present immunotherapy showed significantly longer survival and regression of lung metastases. The mice that received resection of the primary lesion with the additional immunotherapy showed significantly longer survival compared to those treated by surgery alone or immunotherapy alone.  The efficacy of the present immune therapy was dependent on residual tumor burden. On the other hand, pathological review of pediatric cancer tissues showed little expression of immune check-point protein and its related molecules at every stage of the treatment.  The present study indicated the efficacy of immunotherapy with immune activation in pediatric cancers.

研究種目 : 基盤研究 (B) (一般)
研究期間 : 2017～2020
課題番号 : 17H04355
研究分野 : 医学