| Project/Area Number |
19K21359
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| Project/Area Number (Other) |
18H06267 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0906:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
Okano Shinji 福岡歯科大学, 口腔歯学部, 准教授 (10380429)
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 癌免疫療法 / 免疫チェックポイント阻害剤 / 癌集学的治療 / 癌抗原特異的T細胞 / 癌ゲノム不安定性 / PD-1 / 腫瘍免疫 / T細胞 / 化学療法 |
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| Outline of Research at the Start |
免疫チェックポイント阻害剤を用いた集学的治療は患者さんの予後の改善に寄与すると考えられるが、免疫チェックポイント阻害剤と現行の集学的治療との交互作用、特に癌組織のみならず腫瘍抗原特異的T細胞への影響に関する基礎的・臨床的知見が不足しており、その解明が緊急的課題となっている。本研究では、マウス消化器癌腫瘍モデル及びヒト消化器癌組織と患者自身の免疫担当細胞を用いて、各癌腫の標準的化学療法とチェックポイント阻害剤併用療法（がん免疫複合療法）の抗腫瘍効果の詳細な分子機序を解明し、併用薬剤の選択法、投与量、時期の基本原理原則を明らかにし、奏功性の高いがん免疫複合療法を開発する基盤を作る。
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| Outline of Final Research Achievements |
It is important to obtain knowledge about interaction between immune checkpoint inhibitors (ICs) and current standard cancer treatments in combined cancer immunotherapy (CCI).We assessed mechanisms of antitumor effects in the CCI and basic principle for the administration timing of combined drugs using mouse colon adenocarcinoma models. The chemotherapy induced immunogenic cancer cell death and tumor-specific cytotoxic T lymphocytes (TC) responses, and dramatically increased numbers of IFN-gamma producing CD4 and CD8 T cells and TC within the tumors, suggesting that the administration order of the chemotherapy followed by the anti-PD-1 antibody was important (anti-PD-1 treatment was essential for in vivo anti-tumor effects by TC).Chemotherapy reduced not only tumor cell numbers, but also numbers of myeloid-derived suppressor cells and TC. Development of drugs to selectively induce cell death of specific target cells is a promising strategy for new CCIs.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫原性癌細胞死から腫瘍抗原特異的T細胞誘導及び抗腫瘍効果に至る「殺細胞治療関連がん免疫サイクル」を考慮に入れた効率の良いがん複合免疫療法の投与レジメ検討の提唱と新規がん免疫複合療法の開発の一つの標的を提案することができ、がん患者の予後改善のために本研究分野の更なる推進と応用が期待されることを示すことができた。
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