Preclinical study of near-infrared photoimmunotherapy for pancreatic cancer that incorporates nanoparticulate TLR9 agonist K3-SPG
Project/Area Number |
20K08329
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | The Tazuke Kofukai (2022) Kyoto University (2020-2021) |
Principal Investigator |
Ken Takahashi 公益財団法人田附興風会, 医学研究所 腫瘍研究部, 研究員 (60594372)
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Co-Investigator(Kenkyū-buntansha) |
石井 健 東京大学, 医科学研究所, 教授 (00448086)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | がん免疫 / 自然免疫 / TLR9 / 光免疫療法 / ワクチン / 膵癌 / 消化器がん |
Outline of Research at the Start |
申請者は、腫瘍局所の自然免疫活性化(Local Innate Immune Activation: LIIA)を最大化すべく、ナノ粒子TLR9リガンド K3-SPG を用いたin situワクチンの開発を目指してきた。一方、光免疫療法は腫瘍局所の癌抗原放出効果(Local Tumor Antigen Release: LTAR)に優れ、さらに経静脈投与(iv)されたナノ粒子の腫瘍部への集積を亢進させる。本研究では、光免疫とK3-SPG-ivの併用によりLTARとLIIAを最大化し、病変への光照射のみで穿刺を要さない、簡便、安全、かつ効果的な膵癌に対するin situワクチンの開発を目指す。
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Outline of Final Research Achievements |
In situ vaccine (ISV), which activates innate immunity and/or promotes the release of cancer antigens at the tumor site, evokes cancer immunity. Based on our previous findings that ISV using unique TLR9 ligand K3-SPG (K3-SPG-ISV) induces antitumor immunity, here we aimed at testing the hypothesis that near-infrared photoimmunotherapy (NIR-PIT) can be an ideal partner of K3-PSG-ISV by providing vaccine antigens. We showed synergistic antitumor effects of K3-SPG-ISV and CD44-targeting NIR-PIT in the pancreatic cancer model. This combination had systemic antitumor effects, induced immunological memory, and enhanced PD-1 blockade therapy. Mechanistically, we observed intratumoral upregulation of IFN-related genes as well as decreased antitumor effect by CD8 T cell depletion, suggesting the possible roles of IFN and cytotoxic T cell response. In summary, our research highlighted the potential of a novel ISV strategy incorporating NIR-PIT and K3-SPG as a next-generation cancer immunotherapy.
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Academic Significance and Societal Importance of the Research Achievements |
膵癌は消化器癌のなかでも患者数、年間死亡数ともに多く、治療開発のニーズが高い。免疫療法は化学療法と異なり免疫記憶により治療終了後も長期にわたる 再発抑制効果が期待できる優位性があるが、現在の免疫療法の主流であるチェックポイント阻害剤の成績は十分とはいえない。本研究の自然免疫アジュバントを用いたISVと光免疫療法の組み合わせ戦略は、腫瘍をワクチン抗原のソースに転化し免疫誘導を最大化できるため、進行癌に対する治療目的のみでなく、術前免疫療法として実施することで術後再発を効果的に抑制しうる可能性があり、新たな免疫療法の選択肢となることが期待できる。
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy2022
Author(s)
Okada H, Takahashi K, Yaku H, Kobiyama K, Iwaisako K, Zhao X, Shiokawa M, Uza N, Kodama Y, Ishii KJ, Seno H.
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Journal Title
Sci Rep.
Volume: 12
Issue: 1
Pages: 2132-2132
DOI
Related Report
Peer Reviewed / Open Access
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