| Project/Area Number |
17K16058
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Saitama Medical University |
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Principal Investigator |
mouri atsuto 埼玉医科大学, 医学部, 助教 (20774657)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 免疫チェックポイント阻害薬 / 治療奏効例 / 切除不能進行期非小細胞性肺癌 / 免疫関連有害事象 / 投与中止 / 休薬 / 治療奏功例 / ニボルマブ / 免疫阻害薬 / 免疫チェックポイント / 投与間隔 / 拡大 / アルゴリズム / 非小細胞性肺癌 / 免疫療法 |
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| Outline of Final Research Achievements |
Because to enlarge dose interval with immune check point inhibitor(ICI) for patients with Non-small cell lung carcinoma is off-label use, our objects were changed to elucidate the prognosis of NSCLC patients who had once responded to anti-PD-1 therapy and discontinued it and to asses peripheral blood mononuclear cell(PBMC) in patients with long-lasting antitumor immunity after PD-1 blockade therapy.
The patients who discontinued nivolumab therapy due to immune-related adeverse event(irAE) well responded to the retreatment without irAE exacerbation but the prognostic significant difference was not recognized in comparison with the patients who continued off treatment after ir AE cesastion. The patient gathered durable response in spite of a few administration of ICI.CD4+ Tcells with down-regulated expression of CD62L (CD62Llow) in PBMC were rich in patients persisted to obtain response. Possibility to asses PBMC as predict marker of prognosis was demonstrated.
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| Academic Significance and Societal Importance of the Research Achievements |
肺癌だけでなく多くの癌腫に対して有効性をもたらした免疫チェックポイント阻害薬治療の予後予測については未だ不明である。有害事象などにより投与中止となった場合に有害事象回復後に投薬を再開すべきかどうかについては明確な指針がない。今回の研究にて休薬後の再投与における安全性と有効性を評価することができた。また、経時的な末梢血液検体採取にてリンパ球表面抗原を評価することで、効果維持できているものと、効果不良となる症例の全身的な免疫状態の違いを見出した。解析症例数を増やし免疫チェックポイント阻害薬治療の有効性維持の要因を究明し、投与不要症例や効果不良時の治療シークエンスを開発する。
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