2023 Fiscal Year Final Research Report
Improvement of efficiency and safety of solid-cancer selective DDS with Bifidobacterium
| Project/Area Number |
21K06613
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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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| Review Section |
Basic Section 47050:Environmental and natural pharmaceutical resources-related
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| Research Institution | Kagoshima University (2022-2023)
Shinshu University (2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
肥田 重明 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (10345762)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ビフィズス菌 / 固形がん / DDS / 免疫学的安全性 / サイトカイン / 炎症 |
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| Outline of Final Research Achievements |
We investigated the immune response of Bifidobacteria (B) used in DDS. Immune cell activation was evaluated using mouse BMDC (cultured with bovine serum). Bacterium B induced IL-6 and IL-12p40 in a TLR2-dependent manner, but the levels were extremely low compared to Staphylococcus aureus and E. coli, and the induction ability was further weakened in the presence of host serum. When B bacteria was administered intravenously to tumor-bearing mice, the amount of cytokines in the blood was the same as that of the control group, the number and proportion of various cells remained unchanged, and there was no systemic inflammation. From the above,the immunological safety of bacterium B was suggested, not meaning that it never induces an immune reaction at all. In the future, we would like to aim for a more reliable and immunologically safe DDS tool by chemically modifying the surface of B bacteria and creating genetically modified B bacteria.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
がん治療においては、抗体医薬を始めとする様々な分子標的薬の開発がなされ、飛躍的進歩を遂げている。しかし、従来と質の異なる副作用、がんの不均一性による耐性細胞の出現、高薬価などに対する対応策が必要である。これらの問題点を解決するために、がんの嫌気的環境に着目しビフィズス菌を用いて制がん剤を腫瘍局所で持続的産生する系を樹立し、前臨床試験を経て第１相臨床試験まで進んだ。現在までの結果からは、安全性が示唆されるが、その詳細な理由は未解明であり、感染免疫学的に興味深い。安全性をさらに担保するためには免疫的解析が重要であるが、本研究による分子免疫学的安全性の裏付けの進展は免疫学的、社会的に意義深いと思う。
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