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RNA vaccine that exerts antitumor effect via non-canonical antigen presentation pathway

Research Project

Project/Area Number 19K07782
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionJikei University School of Medicine

Principal Investigator

ITO MASAKI  東京慈恵会医科大学, 医学部, 講師 (80297366)

Co-Investigator(Kenkyū-buntansha) 小井戸 薫雄  東京慈恵会医科大学, 医学部, 教授 (70266617)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsRNAワクチン / ワクチン / がん / ネオエピトープ / ネオアンチゲン / 抗原提示経路 / 人工抗原 / mRNA / WT1 / 細胞性免疫 / 腫瘍免疫 / がんワクチン / non-canonical抗原提示経路 / ER-Golgi非依存性経路
Outline of Research at the Start

我々はnon-canonical抗原提示経路を経るように抗原の運命を指定することができる「Artificial Designed Sequence (ADS)」ペプチド配列構造を創製した。本研究では、このADSとB16-F10マウスメラノーマ細胞のネオエピトープ(Obsl1 T1764M)などを、RNAワクチンの枠組みに組み込みRNAワクチンを作製する。RNAワクチンの免疫賦活化能力をin vitro、 in vivoの両面から定量的に評価し、ネオエピトープがnon-canonical抗原提示経路で処理される事によって、腫瘍免疫能力を増大させ、強力に抗腫瘍効果を発揮できる事を明らかにする。

Outline of Final Research Achievements

We have identified an "Artificial Designed Sequence (ADS)" peptide sequence structure that specifies the fate of the antigen to go through the non-canonical antigen presentation pathway (ER-Golgi independent pathway). This ADS and neoepitope of cancer cells were incorporated into the framework of mRNA to prepare an RNA vaccine by implanting a cap analog structure, pseudouridine, and poly-A tail into mRNA using an in vitro transcription system. The immunostimulatory ability of the RNA vaccine was quantitatively evaluated using reporter T cells with neoepitope recognition-specific TCR. It was clarified that the ADS-containing RNA vaccine can efficiently exert cell-mediated immunity induction.

Academic Significance and Societal Importance of the Research Achievements

新型コロナ感染症の世界的パンデミックが起こり、様々な抗原に対して迅速にワクチン製造が可能なRNAワクチンの有効性が実証された。しかしながら、現状のRNAワクチンは抗原の全長mRNAを用いており、今後さらにワクチン効力の改善が求められる。我々の開発しているnon-canonical抗原提示経路を経て抗原提示するワクチンは、RNAワクチンに新たな機能を付与する事が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (1 results)

All 2019

All Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Induction of Wilms tumor 1 (WT1)-specific cytotoxic lymphocytes by artificial antigen vaccine2019

    • Author(s)
      伊藤正紀、小井戸薫雄、芝清隆
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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