Innovative novel cancer vaccine therapy with XCR1 positive dendritic cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18101
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Mizumoto Yuki 和歌山県立医科大学, 医学部, 学内助教 (60596980)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がんワクチン / 樹状細胞 / CTL / 免疫チェックポイント

Outline of Final Research Achievements

XCR+ dendritic cells are professional antigen presenting cells with high CTL-inducing ability. To induce suitable antigen specific immune responses via dendritic cells, simultaneous treatment of anting and adjuvant is quite important. We have prepared XCL1-peptide vaccine in which XCL1, a ligand for chemokine receptor XCR1, is fused with a cancer antigen peptide. Treatment of XCL1-peptide vaccine with adjuvant (poly(I:C)) could strongly induce antigen specific CTL in mice. When dendritic cells were stimulated with XCL1-peptide vaccine and poly(I:C), immune checkpoint molecules were induced along with activation of dendritic cells.
These results suggest that this vaccine can efficiently induce anti-cancer CTLs in combination with immune checkpoint inhibitors.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究により、がん免疫療法で重要となるCTLを生体内で効率的に誘導するシステムとして、XCR1+樹状細胞へのがん抗原の特異的な送達が重要であること、またアジュバント併用による免疫チェックポイント分子の発現から、がんペプチドワクチン療法と免疫チェックポイント阻害剤との併用の有用性が示唆された。マウス実験の結果をヒトへ応用するにあたり、実際的な副作用の発現の有無の検討などの課題があるが、今後のがん免疫療法に対する基礎的なデータが得られたと考えられる。