Control of pediatric cancer cell proliferation by targetting immune checkpoint proteins

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04355
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Keio University
• Principal Investigator: KURODA Tatsuo 慶應義塾大学, 医学部(信濃町), 教授 (60170130)
• Co-Investigator(Kenkyū-buntansha): 田口 智章 福岡医療短期大学, 歯科衛生学科, 学長 (20197247) ; 渕本 康史 慶應義塾大学, 医学部(信濃町), 特任教授 (40219077) ; 大喜多 肇 慶應義塾大学, 医学部(信濃町), 准教授 (50317260) ; 清水 隆弘 慶應義塾大学, 医学部(信濃町), 助教 (80626705)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 小児がん / 免疫チェックポイント蛋白 / 免疫療法 / 腫瘍幹細胞

Outline of Final Research Achievements

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.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

従来、PD1,PDL1の発現や細胞表面抗原の変異が少ないために免疫チェックポイント蛋白阻害療法の効果に疑問がもたれていた小児がんで、免疫賦活を併用することでこの免疫療法が有用であることを示した点で大きな意義があると考える。また従来は原発巣の切除は転移装が制御された場合に適応とされていたが、免疫療法を組み合わせることにより、腫瘍残存量を基盤に小児がん集学的治療の組み立てを根幹から見直させる大きな意義をもつものと考えられた。