Development of novel designer bacteria for cancer therapy based on organic acid-secreting bacteria

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20819
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Nagasaki University (2023); Institute of Physical and Chemical Research (2021-2022)
• Principal Investigator: Nomura Shoko 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (40911178)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: 生菌製剤 / デザイナー細菌 / がん治療 / Blautia coccoides

Outline of Final Research Achievements

The purpose of this study was to investigate organic acid-secreting bacteria useful for cancer therapy from among the predominant bacteria of the mammalian intestinal microbiota and to develop new designer bacteria by introducing a foreign gene expression system to these bacteria. Intravenously administered Blautia coccoides secreting acetic acid and lactic acid as metabolites, and Bacteroides vulgatus, which are the most dominant bacteria in the human intestinal microbiota, showed growth and proliferation in tumors. Particularly, B. coccides showed one-million-fold growth in two weeks in tumors, but did not survive in major organs and showed low host immunogenicity. This indicates that B. coccides is a promising candidate for live bacterial therapeutics for cancer treatment showing both tumor-selective growth and low immunostimulatory activity.

Free Research Field

薬物動態学、腫瘍治療学

Academic Significance and Societal Importance of the Research Achievements

本研究は、生菌製剤を用いたがん治療において、有用な細菌種を開拓し、新規のデザイナー細菌を開発することを目的としている。生菌製剤として前例のない、ヒト腸内細菌叢最優勢の有機酸分泌細菌が、腫瘍内増殖・投与時の安全性を両立する新たな候補細菌種であることを明らかにできた。本研究の成果は、がん治療用生菌製剤の開発において、治療効果と生体適合性の両方を高めたデザイナー細菌の候補細菌種の裾野の拡張に繋がると期待できる。