Development of nanoDDS for cancer therapy without anti-cancer drug: Proposal of RISET therapy and its therapeutic function

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22948
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Chiba University
• Principal Investigator: Akita Hidetaka 千葉大学, 大学院薬学研究院, 教授 (80344472)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 癌治療 / 抗炎症薬 / 脾臓 / 癌免疫

Outline of Final Research Achievements

In this study, we proposed "Reprogramming of Immuno-reaction in Spleen and Extra-parenchyma in Tumor (RISET) therapy" as a new cancer treatment strategy by normalizing antitumor immunity via targeting the inflammatory environment of the spleen. When nanoparticles modified with a water-soluble polymer were loaded with a lipid derivative of an anti-inflammatory drug, and administered to cancer-bearing mice, the tumor volume was significantly reduced. It was clarified that the therapeutic effect of this particle is exerted through the decrease of immunosuppressive cell group in the spleen. Furthermore, when this particle was used in combination with an immune checkpoint inhibitor, a remarkable therapeutic effect was observed in the combination group, demonstrating its usefulness in combination with existing drugs.

Free Research Field

薬剤学

Academic Significance and Societal Importance of the Research Achievements

従来のナノ粒子を用いたがん治療戦略は、がん細胞に対して殺細胞効果を持った抗がん剤を効率的に送達することが重要視されていた。しかしながら、ヒト臨床試験のメタ解析により、EPR効果を利用したがん標的化の実用性に疑問が投げかけられ、根本的な技術改革が必要となった。本研究では上記の古典的な戦略を一新させる戦略として、抗がん剤を使わず、癌細胞を標的としないナノＤＤＳ技術を確立した。また、免疫チェックポイント阻害剤は約30%の患者しか有効性が認めらないという問題を抱えている。RISET戦略は免疫チャックポイント阻害剤との併用療法で高い治療効果を発揮したため、本問題点の解決策となり得る。