Development of the new cancer immunotherapy using iPS-DC which inhibited immune checkpoint

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10521
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Wakayama Medical University
• Principal Investigator: Nakamura Masaki 和歌山県立医科大学, 医学部, 准教授 (80364090)
• Co-Investigator(Kenkyū-buntansha): 中森 幹人 和歌山県立医科大学, 医学部, 非常勤講師 (10322372) ; 山上 裕機 和歌山県立医科大学, 医学部, 教授 (20191190) ; 尾島 敏康 和歌山県立医科大学, 医学部, 講師 (60448785)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 樹状細胞 / iPS細胞 / 癌免疫療法

Outline of Final Research Achievements

In the present study, we induced the iPSDCs from gastrointestinal solid cancer patients, and compared those iPSCs with MoDC from those patients. Moreover, we improved cancer peptide vaccination by targeting Ag peptides selectively to a DC subset, XCR1-expressing DCs (XCR1+ DCs), with high ability to support CD8+ T-cell responses. We have generated a fusion protein, consisting of an Ag peptide presented with MHC class I, and an XCR1 ligand, XCL1, and examined its effects on antitumour immunity in mice. Our results showed that the iPSCs from gastrointestinal solid cancer patients had increased cytokine production and migration ability compared to MoDC from those patients. Moreover, we showed that the fusion protein plus poly(I:C) inhibited the tumor growth efficiently in the prophylactic and therapeutic tumor models. Furthermore, the fusion protein plus poly(I:C) showed suppressive effects on tumor growth in synergy with anti-PD-1 Ab.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、消化器固形癌患者から樹立したiPS細胞からDC（iPSDC）を分化誘導し、その機能を明らかにした。さらに細胞傷害性T細胞(CTL)誘導能の高いペプチドワクチンの作成に成功し、免疫チェックポイント阻害併用による腫瘍増殖抑制の上乗せ効果を証明した。本研究の結果は、ヒト消化器癌に対する免疫チェックポイント阻害機構を併用したDCワクチン療法の臨床応用を立ち上げることにおいて極めて重要な根拠となると考える。