A novel strategy for a cancer immunotherapy and infectious disease treatment using microbial antigen-presenting exosomes

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K01394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Osaka Prefecture University
• 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)
• Project Period (FY): 2016-04-01 – 2020-03-31
• 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

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.

Free Research Field

複合領域

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。