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

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07782
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Jikei 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
• Keywords: RNA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

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.

Free Research Field

腫瘍免疫学

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。