The establishment of a novel cancer therapy utilizing M1 macrophage derived exosomes from patients

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20969
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Shimizu Aasa 大阪大学, 大学院医学系研究科, 招へい教員 (10910268)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 卵巣がん / T細胞活性化 / エクソソーム / THP-1 / M1マクロファージ

Outline of Final Research Achievements

Exosomes can be a future drug carrier for cancer treatment, considering its specificity to cancer cells and evasion ability from immune responses. However, how to collect ample amounts of exosomes from patients remains a critical issue. Herein, we focused peripheral blood as a source of exosomes. First, we confirmed that monocytes can be cultured from peripheral blood of healthy volunteers. However, since the number of cells was not sufficient, we utilized the monocyte-derived cell line THP-1 for the collection of M1 macrophage derived exosomes. We analyzed its role by focusing on the direct effect on ovarian cancer cells and the T cell activation. M1 macrophage derived exosomes showed cytotoxicity against cancer cells. In a co-culture experiment of cancer cells and T cells, we presented that the addition of exosomes activates T cells and increases the cytotoxicity of cancer cells. In conclusion, we demonstrated the future efficacy of M1 macrophage derived exosomes for cancer therapy.

Free Research Field

産婦人科　婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究では患者血液由来のエクソソームの癌治療への可能性を検討した。エクソソームの臨床応用のためには、必要時に患者から必要な量のエクソソームを抽出できることが望ましく、末梢血より腫瘍抑制的に働くエクソソームを分泌する細胞だけを分離培養しエクソソームを抽出する方法を考案した。いくつかのPreclinicalな報告はあるものの“治療用エクソソーム”はまだ世界中のどこでも実現していない。我々の研究はその先鞭をつけるものであると考えており、学術的意義は大きく今後さらなる発展が期待できる研究分野である。