Development of effective combined immunotherapies by using a novel immune response detection method

• Project/Area Number: 16K07168
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Mie University
• Principal Investigator: Miyahara Yoshihiro 三重大学, 医学系研究科, 准教授 (10582083)
• Co-Investigator(Kenkyū-buntansha): 原田 直純 三重大学, 医学系研究科, 特任講師(研究担当) (40520961)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 変異抗原 / 複合免疫療法 / 免疫応答 / ワクチン

Outline of Final Research Achievements

We successfully identified a mutated antigen (mutated Snd1 derived epitope peptide; YAPCRGEF ) that actually elicits an robust immune response in CMS7 tumor-bearing mice by utilizing a newly developed immune response detection method. Furthermore, we confirmed not only the superiority of the newly developed immune response detection method to the conventional method but also mSnd1 long-peptide vaccination has a therapeutic effect, that is, the immune response to mSnd1 causes tumor regression. The CMS7 tumor-bearing mouse model and the novel immune response detection method established in this research are considered to be important bases for the development of effective combined immunotherapy in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究開発において樹立したマウス腫瘍細胞株CMS7担癌マウスにおける変異型Snd1ペプチドへの免疫応答モデルは、今後に期待される治療効果の高い複合免疫療法開発への重要な基盤になると考えられ、学術的意義が高いと考えられる。また、今後益々、個別化がん治療が進展していくと考えられるが、その際には本研究開発で確立した迅速・鋭敏な免疫応答測定法が個々の患者の高免疫原性変異抗原の同定に役立つことも十分に予想され、社会的意義も大きいと考えられる。

Research Products

• [Journal Article] Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance (2019)
  • Author(s): Muraoka Daisuke、Seo Naohiro、Hayashi Tae、Tahara Yoshiro、Fujii Keisuke、Tawara Isao、Miyahara Yoshihiro、Okamori Kana、Yagita Hideo、Imoto Seiya、Yamaguchi Rui、Komura Mitsuhiro、Miyano Satoru、Goto Masahiro、Sawada Shin-ichi、Asai Akira、Ikeda Hiroaki、Akiyoshi Kazunari、Harada Naozumi、Shiku Hiroshi
  • Journal Title: Journal of Clinical Investigation Volume: 129 Issue: 3 Pages: 1278-1294
  • DOI: 10.1172/jci97642
  • NAID: 120006987781
  • Peer Reviewed / Open Access
• [Journal Article] Identification of an immunogenic neo-epitope encoded by mouse sarcoma using CXCR3 ligand mRNAs as sensors (2017)
  • Author(s): Fujii K, Miyahara Y, Harada N, Muraoka D, Komura M, Yamaguchi R, Yagita H, Nakamura J, Sugino S, Okumura S, Imoto S, Miyano S, Shiku H
  • Journal Title: OncoImmunology Volume: 印刷中 Issue: 5 Pages: e1306617-e1306617
  • DOI: 10.1080/2162402x.2017.1306617
  • Peer Reviewed / Open Access
• [Presentation] マウス腫瘍細胞株をモデルとした高免疫原性変異抗原の同定とワクチン治療への応用 (2018)
  • Author(s): 宮原 慶裕
  • Organizer: 第22回日本がん免疫学会総会
• [Presentation] Analysis of TCR repertoire usage and identification of antigens recognized by CT26 tumor-infiltrating CD8+ T cells (2016)
  • Author(s): 藤井 啓介、宮原 慶裕、村岡 大輔、下岡 清美、浜名 洋、岸 裕幸、珠玖 洋
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Determining CD8+ T cell immune responses against the tumor“mutanome”using CXCR3 ligand mRNAs as sensors (2016)
  • Author(s): 宮原 慶裕、藤井 啓介、村岡 大輔、上村 光弘、山口 類、井元 清哉、宮野 悟、珠玖 洋
  • Organizer: 日本がん免疫学
  • Place of Presentation: ひめぎんホール（愛媛県・松山市）
  • Year and Date: 2016-07-30
• [Presentation] CT26 腫瘍局所浸潤CD8+T 細胞のTCRレパトア解析と認識エピトープの同定 (2016)
  • Author(s): 藤井 啓介、宮原 慶裕、村岡 大輔、下岡 清美、浜名 洋、岸 裕幸、珠玖 洋
  • Organizer: 日本がん免疫学
  • Place of Presentation: ひめぎんホール（愛媛県・松山市）
  • Year and Date: 2016-07-30