Development of whole cell cancer vaccine using innate immune-related genes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19449
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Seino Ken-ichiro 北海道大学, 遺伝子病制御研究所, 教授 (20312845)
• Co-Investigator(Kenkyū-buntansha): 和田 はるか 北海道大学, 遺伝子病制御研究所, 准教授 (70392181)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: がんワクチン

Outline of Final Research Achievements

Among cancer immunotherapy, cancer vaccines can potentially prevent recurrent tumors by using the exquisite power and specificity of the immune system. Specifically, whole tumor cell vaccines (WTCVs) based on surgically resected tumors have been considered to elicit robust anti-tumor immune responses by exposing various tumor-associated antigens to host immunity. In this study, we indicate the importance of the interferon regulatory factor 7 (Irf7) axis within tumor cells in regulating immunogenicity. Indeed, WTCVs that augmented the Irf7 axis have exerted remarkable recurrence-preventive effects when vaccinated after tumor inactivation by radiation. The mechanism leading to vaccine effectiveness was mediated by interferon-gamma-producing B cells. This study provides novel insights into how to enhance tumor immunogenicity and use WTCVs as recurrence prophylaxis.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

本研究により、Irf7軸の3因子であるIrf7、Ifi44、Usp18をがん細胞に導入することで、WTCVの再発予防効果を増強できることが明らかになった。Irf7軸がワクチン効果を増強するメカニズムとして、IFNγを産生するB細胞が抗腫瘍免疫応答を増強した。この治療戦略の研究と開発が進めば、がんの再発を予防する新たな治療法が確立され、より多くの患者がこの治療法の恩恵を受けられるようになるかもしれない。これらを総合すると、今回の知見は、がんにおけるIrf7軸を標的とした再発予防がんワクチンの今後の研究を促し、臨床における予防的治療として応用される可能性がある。