Research on the artificial neo-antigen-presenting extracellular vesicles which can activate dendritic cells against tumors

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K01390
• 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: ITO TOMOKO 大阪府立大学, 生命環境科学研究科, 客員研究員 (80372910)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 細胞外小胞 / ネオ抗原 / ガン免疫治療

Outline of Final Research Achievements

Tumor specific mutant neoantigens are essential for successful cancer immunotherapy. However, in most cases, tumors have only non-mutated self-antigens, which possess no or low immunogenicity. To overcome this disadvantage, we have developed a novel "artificial neoantigen strategy".
We prepared extracellular vesicles (EVs) from the cultured cells which had been transfected with plasmid encoding the strong bacterial antigen ESAT-6. The EVs presented ESAT-6 antigen or its epitopes on their surfaces as an "artificial neoantigen".
Those EVs presenting ESAT-6 antigen effectively stimulated the cultured DCs. Injection of the EVs into tumor-bearing mice showed significant antitumour activity. Administration of the DCs stimulated by the EVs also exhibited high antitumor effect in mice. Such "artificial neoantigen"-presenting EVs are expected as novel cancer vaccines.

Free Research Field

DDS

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた微生物抗原提示細胞外小胞は、人工的なネオ抗原として働き抗腫瘍免疫を強制的に効率よく惹起するもので、癌免疫治療の本質的な適応限界を克服する全く新しい戦略を提供する。
本細胞外小胞製剤は患者本人の細胞から調製することができるため、拒絶応答等の副作用や、ウイルス感染等の危険因子を全く含まない安全性の高い製剤である。さらに細胞治療での免疫細胞活性化剤としての利用法は、より安全性の高いヒトへの臨床応用の可能なシステムと期待される。
本研究で得られた知見は「腫瘍細胞の免疫原性の低さ」を克服する癌免疫治療の新しいプラットホーム技術として広く展開でき、癌治療の向上に大きく貢献する。