Cancer microenvironmental remodeling with NO-producing bacterial machine

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K19622
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Nagasaki University (2022); Institute of Physical and Chemical Research (2017-2018)
• Principal Investigator: Mukai Hidefumi 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (60570885)
• Project Period (FY): 2017-06-30 – 2023-03-31
• Keywords: 細胞治療 / 合成生物学 / 細菌 / がん治療 / 一酸化窒素

Outline of Final Research Achievements

We investigated the relationship between bacterial growth in tumors and cancer microenvironmental remodeling, while analyzing the NO-producing ability of mutants of genes involved in NO production. We also developed a novel labeling method of bacteria to evaluate their biodistribution in the body with positron emission tomography. An attenuated strain of Salmonella that successfully grew and functioned in tumors close to human clinical practice induced cancer microenvironmental remodeling, including massive necrosis. It was suggested that the strain may exert unique actions other than increasing tumor vascular permeability.

Free Research Field

ドラッグデリバリーシステム

Academic Significance and Societal Importance of the Research Achievements

嫌気性細菌の一部の種は、静脈内投与後、重篤な副作用なく、腫瘍で選択的に生着・増殖し、この性質を利用した、がんに対するドラッグデリバリーシステム開発が期待される。生体内の材料を使って、必要な場所で、必要な時に、必要な量だけ薬物を作る、薬物の現地生産システムは、薬物治療の新しい潮流の開拓に繋がる。本研究の成果は、がん微小環境リモデリングをトリガーとする、がん治療用デザイナー細菌開発の有用な設計指針を与えるものである。