| Project/Area Number |
20K09431
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Kato Satoshi 金沢大学, 附属病院, 助教 (30584841)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 転移性骨腫瘍 / 凍結療法 / 免疫増強 / 脊椎転移 / 局所凍結療法 / 免疫療法 |
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| Outline of Research at the Start |
転移性骨腫瘍モデルマウスを用いて、生体内の局所凍結療法によるがん特異的免疫増強効果（アブスコパル効果）を検証し、同時にアジュバント物質である免疫チェックポイント阻害剤（抗PD-1抗体）やリポ多糖体（LPS）による相加・相乗効果の有無を明らかにする。さらに臨床例において、転移性脊椎腫瘍に対する液体窒素処理骨移植を併用した根治的手術（腫瘍脊椎骨全摘術）のがん特異的免疫増強効果の検証を行う。
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| Outline of Final Research Achievements |
We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究より、Cryoablationのがん特異的免疫効果と抗PD-1抗体による増強を示した。この結果は骨転移に対する局所治療の意義をさらに高める。骨関連事象に対する手術にCryoablation併用することで、腫瘍の局所制御効果の増強に他の遠隔転移巣に対するがん免疫効果の増強が付加されるHybrid surgeryの開発を目指している。特に、Performance Status低下や手術介入の機会が多い脊椎転移の患者にとっては本研究が目指すHybrid surgery恩恵は大きい。今後はがん免疫上昇効果におけるCryoablationの有利性について他の局所療法を比較検討する予定である。
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