Preclinical study of near-infrared photoimmunotherapy for pancreatic cancer that incorporates nanoparticulate TLR9 agonist K3-SPG

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• 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)
• Co-Investigator(Kenkyū-buntansha): 石井 健 東京大学, 医科学研究所, 教授 (00448086)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん免疫 / 自然免疫 / TLR9 / 光免疫療法

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.

Free Research Field

がん免疫

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。