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Development of innovative delivery systems of biologics to the lung

Research Project

Project/Area Number 18K19935
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionShinshu University (2019)
Yokohama City University (2018)

Principal Investigator

Sato Takashi  信州大学, 先鋭領域融合研究群バイオメディカル研究所, 特任教授 (70510436)

Co-Investigator(Kenkyū-buntansha) 下里 剛士  信州大学, 学術研究院農学系, 教授 (00467200)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords吸入免疫治療 / 肺がん / 乳酸菌 / 遺伝子組換え乳酸菌 / 免疫チェックポイント / PD-1 / 経気道治療 / 吸入療法 / 肺癌免疫療法 / 抗体医薬 / 経気道的治療法 / 高分子医薬 / ナノマイクロ粒子
Outline of Final Research Achievements

Our research focused on the potential therapeutics of the genetically modified Lactic Acid Bacteria (gmLAB) producing biological active molecules that could inhibit disease development/progression. Here we showed that the newly established gmLAB expressing programmed cell death 1 inhibitory single-chain variable fragment could improve survival either by local intranasal or by systemic administration in murine lung cancer model. Among several gmLABs, the use of lactis (L. lactis) has been favored because of 1) generally recognized as safe status, 2) absence of endotoxins, 3) easy manipulating property, and 4) low cost and easy administration. Our L. lactis system, we called “Biological Engineered Medicine” system, demonstrated potential therapeutics for human diseases including lung cancer, and thus we plan to establish as a next generation tool for target therapy.

Academic Significance and Societal Importance of the Research Achievements

本研究では、肺がんの治療としても一般的になった免疫治療の柱である免疫チェックポイント阻害作用に着目し、免疫チェックポイントに関連し抗腫瘍免疫を賦活化しうる低分子の阻害物質を作成するシステムを構築したこと。さらに、低分子の物性により、肺がん病巣への直接送達性を高める経気道投与法の実現可能性を呈示した点に大きな意義がある。また、安全性の高い乳酸菌を用いて安価に大量に産生可能なシステムの開発により、将来の抗体医薬や分子標的医薬のコスト削減を提案し、持続可能な医療保険システムに貢献する社会的意義が大きい研究内容である。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] 米国国立衛生研究所・国立がん研究所/テキサス大学MDアンダーソンがんセンター(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Oral Administration of Flavonifractor plautii Strongly Suppresses Th2 Immune Responses in Mice2020

    • Author(s)
      Ogita Tasuku、Yamamoto Yoshinari、Mikami Ayane、Shigemori Suguru、Sato Takashi、Shimosato Takeshi
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 379-379

    • DOI

      10.3389/fimmu.2020.00379

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The clinical significance of CXCL16 in the treatment of advanced non‐small cell lung cancer2020

    • Author(s)
      Shibata Yuji、Kobayashi Nobuaki、Sato Takashi、Nakashima Kentaro、Kaneko Takeshi
    • Journal Title

      Thoracic Cancer

      Volume: 11 Issue: 5 Pages: 1258-1264

    • DOI

      10.1111/1759-7714.13387

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a New Treatment Modality for Lung Diseases That Uses Innovative Fine Droplet Drying (FDD) Technology Offering Inhalable Nano/microparticles-incorporated Therapeutic Agents2019

    • Author(s)
      Sato T and Shimosato T
    • Journal Title

      Science Impact Ltd.

      Volume: 2019 Issue: 3 Pages: 56-58

    • DOI

      10.21820/23987073.2019.3.56

    • NAID

      120007180880

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Silicosis and lung cancer: current perspectives.2018

    • Author(s)
      Sato T, Shimosato T, Klinman DM
    • Journal Title

      Lung Cancer (Auckl)

      Volume: 9 Pages: 91-101

    • DOI

      10.2147/lctt.s156376

    • NAID

      120007180882

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory role of heme oxygenase-1 in silica-induced lung injury.2018

    • Author(s)
      Nakashima K, Sato T, Shimosato T
    • Journal Title

      Respiratory Research

      Volume: 19 Issue: 1 Pages: 144-144

    • DOI

      10.1186/s12931-018-0852-6

    • NAID

      120007180881

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Innovative therapy for lung cancer ~Intratracheal delivery of nano-microparticles-incorporated immune checkpoint-blocking single-chain variable fragment~2019

    • Author(s)
      Sato T
    • Organizer
      US NIH/NCI Symposium on Innate Immunity & Modulation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 1.抗CTLA-4低分子抗体を産生するLactococcus lactis組換え体の構築2019

    • Author(s)
      村上愛斗, 生井楓, 上田麻未,重盛駿, 荻田佑, 佐藤隆, 下里剛士
    • Organizer
      2019酪農科学シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2.PD-1/PD-L1チェックポイントの阻害に働く乳酸菌組み換え体の構築と肺がんモデルマウスを用いた検証2019

    • Author(s)
      上田麻未,生井楓,村上愛斗,重盛駿,荻田佑,佐藤隆,下里剛士
    • Organizer
      2019酪農科学シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Innovative therapy for lung cancer ~Intratracheal delivery of nanomicroparticles-incorporated immune checkpoint-blocking single-chain variable fragment~2019

    • Author(s)
      Takashi Sato
    • Organizer
      US National Insitute of Health/National Cancer Insitute Seminar
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 吸入治療イノベーション~吸入薬で肺癌の制御を目指す研究開発の取り組み~2018

    • Author(s)
      佐藤 隆
    • Organizer
      横浜市立大学先端医科学研究センター市民講座
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] New Treatment Modality for Lung Diseases

    • URL

      https://www.ingentaconnect.com/content/sil/impact/2019/00002019/00000003/art00022

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Patent(Industrial Property Rights)] 医薬組成物2019

    • Inventor(s)
      佐藤隆、下里剛士、森谷樹、森永匡彦、佐藤祐一、小番昭宏
    • Industrial Property Rights Holder
      佐藤隆、下里剛士、森谷樹、森永匡彦、佐藤祐一、小番昭宏
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas

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Published: 2018-07-25   Modified: 2021-02-19  

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