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Development of novel immune combination therapy for interstitial pneumonia associated with connective tissue disease

Research Project

Project/Area Number 19K08623
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Nakamura Yutaro  浜松医科大学, 医学部附属病院, 講師 (60436962)

Co-Investigator(Kenkyū-buntansha) 須田 隆文  浜松医科大学, 医学部, 教授 (30291397)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords間質性肺炎 / 膠原病 / 樹状細胞 / 樹状細胞療法 / 間質性肺疾患 / 免疫療法 / 間質影肺炎 / 関節リウマチ
Outline of Research at the Start

申請者らは,効率的で優れた樹状細胞(DC)の免疫調節能を利用し,動物モデルで各種腫瘍および感染症に,極めて有望なワクチンを開発してきた.本研究はこれらの技術を応用し,治療選択の極めて限定された膠原病に伴う間質性肺炎に対して,免疫反応を抑える制御性DCおよび免疫チェックポイントの賦活により,治療ワクチンおよび複合免疫療法としての研究基盤を確立することが目的である.肺における過剰な免疫反応を抑制する本研究の実験系は,今後の病態解析にも有用なモデルとなる可能性もあり,極めて発展性の高い研究と考える.

Outline of Final Research Achievements

We aimed to develop a novel therapeutic vaccine for the patients with interstitial pneumonia associated with connective tissue disease, suppressing local inflammation of the lung. We also analyzed the histological findings with human lung specimens from the patients with rheumatoid lung disease (RLD). Eventually we found that fibrotic components might be more important for the prognosis of RLD patients than inflammatory components.

Academic Significance and Societal Importance of the Research Achievements

我々は人の肺の外科的生検検体を用いた検討において,炎症性病態も重要であるが,より線維化病態が予後に与える影響が大きい可能性を示した.これらの結果より現状では,ほぼ炎症性病態のみを標的とした樹状細胞を用いた治療ワクチンの効果は限定的であり,さらに医学的効果のみならず臨床応用後の対費用効果の面からもその有用性は乏しいことが考慮された.以上から引き続き,人,マウスの検体を用いた検討をさらに進め,より効果的な膠原病に伴う間質性肺疾患の治療ターゲットを探索する研究を継続している.

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 7 results) Presentation (3 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model2022

    • Author(s)
      Hozumi Hironao、Kono Masato、Hasegawa Hirotsugu、Kato Shinpei、Inoue Yusuke、Suzuki Yuzo、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Yokomura Koshi、Nakamura Hidenori、Suda Takafumi
    • Journal Title

      Respiratory Research

      Volume: 23 Issue: 1 Pages: 57-57

    • DOI

      10.1186/s12931-022-01978-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simple method for detecting idiopathic interstitial pneumonias by measuring vertical lung length on chest X-ray.2021

    • Author(s)
      Karayama M, Aoshima Y, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suda T.
    • Journal Title

      Sci Rep.

      Volume: 11(1) Issue: 1 Pages: 7669-7669

    • DOI

      10.1038/s41598-021-87452-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia2021

    • Author(s)
      Yamagata Akira、Arita Machiko、Tachibana Hiromasa、Tokioka Fumiaki、Sugimoto Chikatoshi、Sumikawa Hiromitsu、Tanaka Tomonori、Yasui Hideki、Fujisawa Tomoyuki、Nakamura Yutaro、Suda Takafumi、Ishida Tadashi
    • Journal Title

      Respiratory Research

      Volume: 22 Issue: 1 Pages: 115-115

    • DOI

      10.1186/s12931-021-01726-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic significance of peripheral blood monocyte and neutrophil counts in rheumatoid arthritis-associated interstitial lung disease2021

    • Author(s)
      Saku Aiko、Fujisawa Tomoyuki、Nishimoto Koji、Yoshimura Katsuhiro、Hozumi Hironao、Karayama Masato、Suzuki Yuzo、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
    • Journal Title

      Respiratory Medicine

      Volume: 182 Pages: 106420-106420

    • DOI

      10.1016/j.rmed.2021.106420

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: a multicentre retrospective cohort study2021

    • Author(s)
      Suzuki Takahito、Hozumi Hironao、Miyashita Koichi、Kono Masato、Suzuki Yuzo、Karayama Masato、Furuhashi Kazuki、Hasegawa Hirotsugu、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Yokomura Koshi、Nakamura Hidenori、Suda Takafumi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-88718-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic and Clinical Value of Cluster Analysis in Idiopathic Pleuroparenchymal Fibroelastosis Phenotypes2021

    • Author(s)
      Nakamura Yutaro、Mori Kazutaka、Enomoto Yasunori、Kono Masato、Sumikawa Hiromitsu、Johkoh Takeshi、Colby Thomas V.、et al.
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 7 Pages: 1498-1498

    • DOI

      10.3390/jcm10071498

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias2021

    • Author(s)
      Enomoto Noriyuki、Homma Sakae、Inase Naohiko、Kondoh Yasuhiro、Saraya Takeshi et al.
    • Journal Title

      Thorax

      Volume: 77 Issue: 2 Pages: 143-153

    • DOI

      10.1136/thoraxjnl-2020-216263

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study2020

    • Author(s)
      Suzuki Y, Karayama M, Uto T, Fujii M, Matsui T, Asada K, Kusagaya H, Kato M, Matsuda H, Matsuura S, Toyoshima M, Mori K, Ito Y, Koyauchi T, Yasui H, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T.
    • Journal Title

      Journal of Thoracic Oncology

      Volume: S1556 Issue: 8 Pages: 1317-1327

    • DOI

      10.1016/j.jtho.2020.04.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a novel T cell‐oriented vaccine using CTL/Th‐hybrid epitope long peptide and biodegradable microparticles, against an intracellular bacterium2020

    • Author(s)
      Tanaka Kazuki、Enomoto Noriyuki, et al.
    • Journal Title

      Microbiology and Immunology

      Volume: 64 Issue: 10 Pages: 666-678

    • DOI

      10.1111/1348-0421.12836

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of forced vital capacity decline prior to and following antifibrotic therapy in idiopathic pulmonary fibrosis2020

    • Author(s)
      Aono Yuya、Nakamura Yutaro, et al.
    • Journal Title

      Therapeutic Advances in Respiratory Disease

      Volume: 14

    • DOI

      10.1177/1753466620953783

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Frequency and clinical relevance of anti-cyclic citrullinated peptide antibody in idiopathic interstitial pneumonias2019

    • Author(s)
      Katsumata M, Hozumi H, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T.
    • Journal Title

      Respir Med

      Volume: 154 Pages: 102-108

    • DOI

      10.1016/j.rmed.2019.06.016

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone.2019

    • Author(s)
      Kono M, Nakamura Y, Enomoto N, Saito G, Koyanagi Y, Miyashita K, Tsutsumi A, Kobayashi T, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Miki Y, Hashimoto D, Fujisawa T, Inui N, Suda T, Nakamura H.
    • Journal Title

      Respir Investig.

      Volume: 57 Issue: 6 Pages: 552-560

    • DOI

      10.1016/j.resinv.2019.07.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Clinical value of cluster analysis of unclassifiable idiopathic interstitial pneumonias phenotypes.2020

    • Author(s)
      Nakamura Y
    • Organizer
      30th International Congress of the European Respiratory Society
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinical significance of the lower-lobe interstitial lung disease in patients with idiopathic pleuroparenchymal fibroelastosis.2019

    • Author(s)
      Kono M, Nakamura Y, Enomoto N, Fujita Y, Takeda K, Miyashita K, Tsutsumi A, Kobayashi T, Miki Y, Hashimoto D, Suda T, Nakamura H
    • Organizer
      American Thoracic Society International Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prognostic and clinical value of cluster analysis of idiopathic pleuroparenchymal fibroelastosis phenotypes.2019

    • Author(s)
      Nakamura Y, Enomoto Y, Kono M, Satake Y, Sumikawa H, Johkoh T, Colby TV, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Inui N, Iwashita T, Kuroishi S, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Yamada T, Shirai T, Hayakawa H, Suda T
    • Organizer
      European Respiratory Society International Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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