| Project/Area Number |
17K09421
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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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| Research Field |
Gastroenterology
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| Research Institution | Kyoto University |
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Principal Investigator |
TAKAHASHI Ken 京都大学, 医学研究科, 助教 (60594372)
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| Co-Investigator(Kenkyū-buntansha) |
石井 健 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ワクチン・アジュバント研究センター, 招へいプロジェクトリーダー (00448086)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | がん免疫 / 自然免疫 / 消化器癌 / ワクチン / 消化器がん / 肝がん / 肝細胞癌 |
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| Outline of Final Research Achievements |
There is an urgent need for potent cancer immunotherapy for gastrointestinal malignancies. In situ vaccine, intratumoral injection of stimulator of innate immunity, allows for the development of vaccines in patients themselves. The aim of this study was to unveil the antitumor activity of in situ vaccine using novel TLR9 agonist K3-SPG in the preclinical models of gastrointestinal malignancies. Transplantable subcutaneous mouse models for colon and pancreatic cancers were established. In these models, K3-SPG suppressed tumor growth, prolonged survival and synergized with PD-1 blockade. K3-SPG in situ vaccine clearly induced immunological memory and suppressed untreated tumor at the opposite side of treated one. We excluded analysis of hepatocellular carcinoma (HCC) model and utilization of RIG-I agonist both of which were originally included in the experiment plans, because of technical difficulty in establishing HCC model and because of the potent antitumor activity of K3-SPG alone.
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| Academic Significance and Societal Importance of the Research Achievements |
がん免疫療法としてのin situワクチンは、①個々の患者由来のがん抗原をそのまま利用するため煩雑な抗原同定の過程を要さない、②抗原特異性が異なる抗腫瘍T細胞を多数誘導できる、③局所療法なので全身性の副作用が少ない、④局所療法ながら全身性の抗腫瘍免疫を誘導できるなどの利点を有し、理想的な個別化がんワクチン治療となりうる。消化器がんは難治であるが患者数も多く、新規の治療法の開発が期待される。消化器がんは、超音波ガイド下や内視鏡下に腫瘍局所への薬剤注入が可能であり、本研究の成果をもとに自然免疫活性化アジュバントをもちいたin situワクチンの臨床応用が期待される。
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