Construction of PK/PD evaluation system for optimizing treatment using immune checkpoint inhibitors

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Mie University
• Principal Investigator: Iwamoto Takuya 三重大学, 医学部附属病院, 准教授 (30447867)
• Co-Investigator(Kenkyū-buntansha): 奥田 真弘 三重大学, 医学部附属病院, 教授 (70252426)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 免疫チェックポイント阻害薬 / バイオマーカー / がん化学療法

Outline of Final Research Achievements

This study was performed to investigate the association of host factors including peripheral blood cell characteristics with the PD-1/PD-L1 therapy. A total of 20 patients were enrolled. The number of patients administrated pembrolizumab, nivolumab, and atezolizumab was 12, 7 and 1, respectively. Twelve patients were diagnosed as progressive disease (PD), and 8 were non-PD. All 6 female patients were diagnosed as PD. In the blood sample obtained within 3 weeks from the immune therapy, significantly high CD28 positive CD8+ T lymphocyte counts and low neutrophil counts were observed in the non-PD patients compared with the PD patients. Meanwhile, the distribution of tumor PD-L1 levels, clinical stage of NSCLC, and other immune markers investigated in the non-PD patients were comparable with the PD patients. CD28 positive CD8+ T lymphocyte and neutrophil counts were considered to be possible biomarkers related to the efficacy of PD-1/PD-L1 therapy.

Free Research Field

臨床薬理・薬剤学

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、免疫チェックポイント阻害薬 の治療効果や副作用を予測する血液免疫学的因子を明らかにすることであり、それらが明確になれば、免疫チェックポイント阻害薬による治療の良好な適応患者の選別、重篤な副作用回避につながり、がん薬物治療の個別最適化の進展に大きく貢献すると考えられる。また、研究成果は、がん薬物治療の成績向上に直結することはもちろんのこと、治療失敗や副作用による医療費の損失を抑える経済的な観点からも貢献が期待できる。さらに本研究は、がん診療連携拠点病院が実施する社会的意義の高い研究と位置づけられる。