A novel strategy for a cancer immunotherapy and infectious disease treatment using microbial antigen-presenting exosomes
| Project/Area Number |
16K01394
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Koyama Yoshiyuki 大阪府立大学, 生命環境科学研究科, 客員研究員 (00162090)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | エクソソーム / 人工ネオ抗原 / 結核菌抗原 / 抗腫瘍免疫 / 細胞性免疫 / 感染症 / 人工ネオアンティジェン / 人工ネオエピトープ / 樹状細胞 / 抗腫瘍免疫治療 / ESAT-6 / 免疫治療 / ネオアンティジェン / ネオエピトープ / 微生物抗原 / 免疫学 / バイオテクノロジー / ナノバイオ |
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| Outline of Final Research Achievements |
We have developed a novel "artificial neoantigen strategy", where we transformed the tumor cells with a gene encoding for a highly antigenic microbial antigen to induce the protein as an "artificial neoantigen". In vivo transfection with the gene for Mycobacterium tuberculosis antigen, ESAT-6 into tumor cells resulted in a significant inhibition of tumor growth in mice and dogs by both the early innate and following adaptive cellular immune responses.
Transfected tumor cells would secrete exosomes presenting ESAT-6 epitopes (ESAT-Ex). ESAT-Ex would most likely mediate these immune responses. Then we prepared ESAT-Ex from the cultured tumor cells which had been transfected with DNA expressing ESAT-6. Injection of ESAT-Ex into tumor-bearing mice evidently suppressed the tumor growth. Dendritic cells (DCs) were effectively stimulated by ESAT-Ex, and the cultured DCs treated with the exosomes exhibited significantly improved antitumor activity in tumor-bearing mice.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍抗原の免疫原性の低さがガン免疫治療の大きな障壁となっている。本研究は、抗原性の高い微生物抗原を人工ネオ抗原として導入し、この障壁を克服する新たな戦略を提供する。
本研究で創製するエクソソーム製剤はウイルス等を含まない安全な生物製剤である。また、より安全なシステムとして、培養樹状細胞を本エクソソーム製剤で活性化し、樹状細胞のみを患者に戻す新たな治療法を考案しその効果を確認した。さらに同システムは感染症治療にも有効な細胞性免疫活性化機能を持つことを確認した。これらの知見は行き詰まったガン免疫治療を大きく推進させるブレイクスルーとなり、感染症の新しい治療法を提示して国民の福祉、健康に貢献する。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Innate immunity mediated by dendritic cells/macrophages plays a central role in the early period in tumor treatment using gene of Mycobacterium tuberculosis antigen2018
Author(s)
Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K. Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
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Journal Title
Journal of Veterinary Medical Science
Volume: 80
Issue: 2
Pages: 190-196
DOI
NAID
ISSN
0916-7250, 1347-7439
Related Report
Peer Reviewed / Open Access
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