| Project/Area Number |
21K16841
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 頭頸部がん / 腫瘍免疫 / ネオアンチゲン / TCR-T / 頭頸部希少がん / がんワクチン / 中咽頭がん / 頭頸部癌 |
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| Outline of Research at the Start |
頭頸部扁平上皮がん (Head and Neck Squamous Cell Carcinoma: HNSCC) の進行症例は未だ予後不良である。ネオアンチゲンがんワクチン療法は今後の個別化治療の実現にむけた有望な選択肢の一つであるが、HNSCCに対しての効果は未だ確立していない。今回の研究ではHNSCCマウスモデルを用いてネオアンチゲン療法の効果、また抗PD-1抗体との併用について検討する。また、患者由来HNSCC検体を採取し in silicoでネオアンチゲンを予測、候補に対しペプチド合成し患者検体への反応を確認しネオアンチゲンを同定することで、がんワクチン療法臨床応用の可能性を検討する。
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| Outline of Final Research Achievements |
We reported that an overlap antigen containing both MHC-I and MHC-II antigens showed strong antitumor effects in a head and neck cancer mouse model sensitive to anti-PD-1 antibodies (Shibata H et al. Oncoimmunology 2021). We summarized the current status of neoantigen vaccines for head and neck cancer (Shibata H et al. Cancer Sci 2021, Shibata H et al. Front in Oncol 2021). Neoantigen therapy was performed on a head and neck cancer mouse model resistant to anti-PD-1 antibodies. Although it showed temporary antitumor effects, escape tumors soon appeared.
Tissues of oropharyngeal HNSCC and head and neck rare cancers were collected and subjected to RNA-seq and exome-seq to predict neoantigens in silico. We are conducting single-cell RNA analysis and TCR analysis of T cells to identify tumor-specific T cells. TCR derived from T cells with an exhausted phenotype with cytotoxic activity or progenitor cell activity is considered to be promising. Using these data, we are developing TCR-T.
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| Academic Significance and Societal Importance of the Research Achievements |
抗PD-1抗体に感受性の頭頸部がんマウスモデルに対し、MHC-IとMHC-II アンチゲンを両方含むoverlap antigen が強い抗腫瘍効果を示すことを示した(Shibata H et al. Oncoimmunology 2021)。また、ネオアンチゲンワクチンの現状をまとめ報告した(Shibata H et al. Cancer Sci 2021、Shibata H et al. Frontiers in Oncology 2021)。一方で、抗PD-1抗体に抵抗性のがんマウスモデルにはネオアンチゲンワクチンは有意な効果を示さなかった。併用療法やTCR-Tの開発を行い研究を続ける。
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