Identification for biomarkers in cancer peptide vaccine therapy with immune checkpoint inhibitors
Project/Area Number |
18K08681
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Yamaguchi University |
Principal Investigator |
Suzuki Nobuaki 山口大学, 大学院医学系研究科, 講師 (50526910)
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Co-Investigator(Kenkyū-buntansha) |
恒富 亮一 山口大学, 医学部附属病院, 講師 (10420514)
友近 忍 山口大学, 医学部附属病院, 助教 (30403679)
硲 彰一 山口大学, 医学部, 教授(寄附講座等) (50253159)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | ペプチドワクチン療法 / 免疫チェックポイント阻害剤 / バイオマーカー / ペプチドワクチン / 免疫チェックポイント / 負の免疫応答 / 癌局所微小環境 / がんペプチド療法 / 固形がん |
Outline of Final Research Achievements |
Strong infiltration of CD8 + T cells and PD1 + T cells into tumor lesions expressing HSP70 and GPC3 antigens was observed. In addition, as a result of exploratory analysis from mass cytometry (CyTOF), the decrease in T cell exhaustion markers (BTLA and CCR4) of PBMC after vaccination (p = 0.03, p = 0.06), the increase in PD1 expression of TIL, and Granzyme B And low expression of perforin was revealed. It was suggested that this immunotherapy has the function of locally inducing T cells to change from cold tumor to hot tumor. In addition, PD1 expression and immune exhaustion status in TIL were confirmed, and the rationale for the combined use of ICI and this vaccine therapy was obtained as the next novel immunotherapy.
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Academic Significance and Societal Importance of the Research Achievements |
この研究で、固形癌(食道癌、胃癌、大腸癌、肝癌、膵癌、乳癌)に対するこれまでのペプチドワクチン療法と新規ペプチドワクチン療法を比較することにより、各種バイオマーカー(詳細は下段に記載)探索として、免疫染色、flowcytometry、ELISPOTならびにTCR(T細胞抗原認識受容体)レパトワ解析を行い、ペプチドワクチンのバイオマーカーを探索・同定すると同時に、固形癌患者における負の免疫病態を解明し、制御すべき病態を解明する基盤的研究を行う。さらには、免疫チェックポイント阻害剤と本ワクチン療法併用の科学的根拠を導出し、次世代の新規免疫療法として実用可能性を探索する。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Identification of a Promiscuous Epitope Peptide Derived From HSP70.2019
Author(s)
Matsui H, Hazama S, Tamada K, Udaka K, Irie A, Nishimura Y, Miyakawa T, Doi S, Nakajima M, Kanekiyo S, Tokumitsu Y, Shindo Y, Tomochika S, Yoshida S, Iida M, Suzuki N, Takeda S, Yamamoto S, Yoshino S, Ueno T, Nagano H
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Journal Title
J Immunother
Volume: 42
Issue: 7
Pages: 244-250
DOI
Related Report
Peer Reviewed / Open Access
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