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Development of a therapeutic vaccine targeting IL17A for treatment of spondyloarthritis.

Research Project

Project/Area Number 18K09103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionOsaka University

Principal Investigator

Tomita Tetsuya  大阪大学, 医学系研究科, 寄附講座准教授 (30283766)

Co-Investigator(Kenkyū-buntansha) 中神 啓徳  大阪大学, 医学系研究科, 寄附講座教授 (20325369)
二井 数馬  大阪大学, 医学系研究科, 助教 (30588380)
吉川 秀樹  大阪大学, 医学系研究科, 理事・副学長 (60191558)
岡田 随象  大阪大学, 医学系研究科, 教授 (70727411)
玉城 雅史  大阪大学, キャンパスライフ健康支援センター, 助教 (90837535)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords脊椎関節炎 / HLA / B-27 / IL-17A / 療法 / 強直性脊椎炎 / ワクチン / HLA B-27 / ワクチン療法 / HLA B-27 / 体軸生脊椎関節炎 / 疾患関連遺伝子
Outline of Final Research Achievements

Ankylosing spondylitis is major disease of spondyloarthritis (SpA), resulting in ankylosis of the spine with bone erosion and new bone formation. Recently, interleukin (IL) 17A has been focused as a strong mediator for bone disruption and formation. We have been focusing on therapeutic vaccines, by which therapeutic antibodies could be produced individually for long term. In this study, we developed a therapeutic vaccine for ankylosing spondylitis by targeting IL17A and evaluated its pharmacological effect by using SpA model in rats. In this study, we found that IL17A peptide-based vaccine with adjuvant successfully induced antibody production, and suppressed arthritis clinically. X-ray and histological analysis showed that enthesitis, bone destruction were inhibited by vaccine, compared with control. We confirmed that vaccine has no toxic effect on tissues. These suggested that therapeutic vaccine targeting IL17A could be a fascinating therapeutic option for SpA.

Academic Significance and Societal Importance of the Research Achievements

強直性脊椎炎は10-20代に発症し、炎症性背部痛のため就学・就労に大きな支障が生じる。治療として生物学的製剤が使用され、その有効性が高いが、高価であり、頻回の投与が必要である。我々が本研究課題で開発したIL-17A治療ワクチンは疾患モデルではその有効性、安全性が確認できた。今後実用化されれば安価であり、投与回数も半減できることから、同疾患で苦しむ患者には学術的また経済的にもその社会的意義は大きいと考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (40 results)

All 2020 2019 2018

All Journal Article (18 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (21 results) (of which Invited: 15 results) Book (1 results)

  • [Journal Article] Non-radiographic axial spondyloarthritis2020

    • Author(s)
      Kameda Hideto、Kobayashi Shigeto、Tamura Naoto、Kadono Yuho、Tada Kurisu、Yamamura Masahiro、Tomita Tetsuya
    • Journal Title

      Modern Rheumatology

      Volume: 31 Issue: 2 Pages: 277-282

    • DOI

      10.1080/14397595.2020.1830512

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Diagnosis and Treatment of Adult Patients with SAPHO Syndrome: Controversies Revealed in a Multidisciplinary International Survey of Physicians2020

    • Author(s)
      Furer V, Kishimoto M, Tsuji S, Taniguchi Y, Ishihara Y, Tomita T, Helliwell PS, Elkayam O
    • Journal Title

      Rheumatology and Therapy

      Volume: 7 Issue: 4 Pages: 883-891

    • DOI

      10.1007/s40744-020-00235-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials2020

    • Author(s)
      Genovese Mark C、Mysler Eduardo、Tomita Tetsuya、Papp Kim A、Salvarani Carlo、Schwartzman Sergio、Gallo Gaia、Patel Himanshu、Lisse Jeffrey R、Kronbergs Andris、Leage Soyi Liu、Adams David H、Xu Wen、Marzo-Ortega Helena、Lebwohl Mark G
    • Journal Title

      Rheumatology

      Volume: 59 Issue: 12 Pages: 3834-3844

    • DOI

      10.1093/rheumatology/keaa189

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment patterns and health care resource utilization among Japanese patients with ankylosing spondylitis: A hospital claims database analysis2020

    • Author(s)
      Tomita Tetsuya、Sato Masayo、Esterberg Elizabeth、Parikh Rohan C.、Hagimori Kohei、Nakajo Ko
    • Journal Title

      Modern Rheumatology

      Volume: 31 Issue: 2 Pages: 431-441

    • DOI

      10.1080/14397595.2020.1775927

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W).2020

    • Author(s)
      Dougados M, Wei JC, Landewé R, Sieper J, Baraliakos X, Van den Bosch F, Maksymowych WP, Ermann J, Walsh JA, Tomita T, Deodhar A, van der Heijde D, Li X, Zhao F, Bertram CC, Gallo G, Carlier H, Gensler LS; COAST-V and COAST-W Study Groups.
    • Journal Title

      Ann Rheum Dis.

      Volume: 79 Issue: 2 Pages: 176-185

    • DOI

      10.1136/annrheumdis-2019-216118

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial.2020

    • Author(s)
      Deodhar A, van der Heijde D, Gensler LS, Kim TH, Maksymowych WP, Østergaard M, Poddubnyy D, Marzo-Ortega H, Bessette L, Tomita T, Leung A, Hojnik M, Gallo G, Li X, Adams D, Carlier H, Sieper J; COAST-X Study Group.
    • Journal Title

      Lancet

      Volume: 395 Issue: 10217 Pages: 53-64

    • DOI

      10.1016/s0140-6736(19)32971-x

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] "総説 特集:脊椎関節炎―診療のABCから最新の話題まで乾癬性関節炎―治療"2020

    • Author(s)
      辻成佳、冨田哲也
    • Journal Title

      日本脊椎関節炎学会誌

      Volume: 7 Pages: 35-45

    • Related Report
      2020 Annual Research Report
  • [Journal Article] "総説 特集:脊椎関節炎― 診療のABCから最新の話題まで体軸性脊椎関節炎―診療と診断"2020

    • Author(s)
      冨田哲也、辻成佳
    • Journal Title

      日本脊椎関節炎学会誌

      Volume: 7 Pages: 3-7

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 総説 体軸性脊椎関節炎に対するイキセキズマブの薬理学的特性ならびに有効性・安全性2020

    • Author(s)
      多田久里守、萩森恒平、許斐綾子、中條航、冨田哲也
    • Journal Title

      新薬と臨牀

      Volume: 69 Pages: 1046-1065

    • Related Report
      2020 Annual Research Report
  • [Journal Article] SAPHO症候群/慢性再発性多発性骨髄炎(CRMO)2020

    • Author(s)
      辻成佳、野口貴明、橋本淳、冨田哲也
    • Journal Title

      リウマチ科

      Volume: 62 Pages: 148-156

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 治療法の再整理とアップデートのために 専門家による私の治療 強直性脊椎炎2020

    • Author(s)
      冨田 哲也
    • Journal Title

      WEB医事新報

      Volume: 5013 Pages: 148-156

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 脊椎関節炎の分類2020

    • Author(s)
      冨田哲也、辻成佳、玉城雅史
    • Journal Title

      関節外科

      Volume: 39 Pages: 364-369

    • Related Report
      2020 Annual Research Report
  • [Journal Article] SAPHO症候群の診断と治療2020

    • Author(s)
      辻成佳、岸本暢将、森田明理、冨田哲也、野口貴明、橋本 淳
    • Journal Title

      関節外科

      Volume: 39 Pages: 387-393

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Filgotinibの強直性脊椎炎に対する効果2020

    • Author(s)
      冨田哲也、辻成佳、玉城雅史
    • Journal Title

      リウマチ科

      Volume: 63 Pages: 443-448

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Clinical Characteristics of Patients with Spondyloarthritis in Japan in Comparison with Other Regions of the World.2019

    • Author(s)
      Kishimoto M, Yoshida K, Ichikawa N, Inoue H, Kaneko Y, Kawasaki T, Matsui K, Morita M, Suda M, Tada K, Takizawa N, Tamura N, Taniguchi A, Taniguchi Y, Tsuji S, Haji Y, Rokutanda R, Yanaoka H, Cheung PP, Gu J, Kim TH, Luo SF, Okada M, López Medina C, Molto A, Dougados M, Kobayashi S, van der Heijde D, Tomita T.
    • Journal Title

      J Rheumatol.

      Volume: 46 Issue: 8 Pages: 896-903

    • DOI

      10.3899/jrheum.180412

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 強直性脊椎炎2019

    • Author(s)
      冨田哲也、辻成佳
    • Journal Title

      日本臨床

      Volume: 77 Pages: 510-515

    • Related Report
      2019 Research-status Report
  • [Journal Article] 炎症性腸疾患に伴う脊椎関節炎2019

    • Author(s)
      冨田哲也
    • Journal Title

      Pharma Medica

      Volume: 37 Pages: 63-65

    • Related Report
      2019 Research-status Report
  • [Journal Article] xekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial.2018

    • Author(s)
      van der Heijde D, Cheng-Chung Wei J, Dougados M, Mease P, Deodhar A, Maksymowych WP, Van den Bosch F, Sieper J, Tomita T, Landewé R, Zhao F, Krishnan E, Adams DH, Pangallo B, Carlier H; COAST-V study group.
    • Journal Title

      Lancet

      Volume: 392 Issue: 10163 Pages: 2441-2451

    • DOI

      10.1016/s0140-6736(18)31946-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] X線基準を満たさない体軸性脊椎関節炎に対する抗TNF製剤の治療成績2020

    • Author(s)
      冨田哲也、松原優里、中村好一
    • Organizer
      第30回日本脊椎関節炎学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 強直性脊椎炎と類縁疾患 生物学的製剤未使用又はTNF阻害薬で効果不十分又は忍容不良(TNFi-IR)の活動性の強直性脊椎炎(AS、X線所見のある体軸性脊椎関節炎)患者に対するイキセキズマブ(IXE)52週投与時の有効性及び安全性 COAST-V試験、COAST-W試験2020

    • Author(s)
      冨田哲也
    • Organizer
      第64回日本リウマチ学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 強直性脊椎炎と類縁疾患 X線基準を満たさない体軸性脊椎関節炎患者でのイキセキズマブの有効性及び安全性 COAST-X、第3相、無作為化、プラセボ対照試験2020

    • Author(s)
      多田久里守、許斐綾子、中條航、Leung AnnAdams David、Carlier Hilde、冨田哲也
    • Organizer
      第64回日本リウマチ学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 体軸性脊椎関節炎の課題2020

    • Author(s)
      冨田哲也
    • Organizer
      第7回JCRベーシックリサーチカンファレンス
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 日本における体軸性SpA診断の現状と課題2020

    • Author(s)
      冨田哲也
    • Organizer
      第93回日本整形外科学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脊椎関節炎の診療IBD関連SpAの治療2020

    • Author(s)
      冨田哲也
    • Organizer
      第64回日本リウマチ学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脊椎関節炎の診断と治療2020

    • Author(s)
      冨田哲也
    • Organizer
      第64回日本リウマチ学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 本邦における体軸性脊椎関節炎診療の課題2020

    • Author(s)
      冨田哲也
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 強直性脊椎炎に対する抗体産生誘導型ワクチンの開発2020

    • Author(s)
      冨田哲也、孫嬌、柳田結花、林宏樹、森下竜一、中神啓徳
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 体軸性脊椎関節炎の最近の動向と今後の展開2020

    • Author(s)
      冨田哲也、松原優里、辻成佳、玉城雅史、中村好一
    • Organizer
      第134回中部日本整形外科災害外科学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] non-radiographic(X線基準を満たさない)axialSpAの本邦での現状2019

    • Author(s)
      冨田哲也
    • Organizer
      第63回日本リウマチ学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 活動性の強直性脊椎炎(X線所見のある体軸性脊椎関節炎)患者に対するイキセキズマブの有効性及び安全性(16週):第3相無作為化プラセボ・実薬対照COAST-V試験2019

    • Author(s)
      冨田哲也
    • Organizer
      第63回日本リウマチ学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 強直性脊椎関節炎全国疫学調査2019

    • Author(s)
      冨田哲也
    • Organizer
      第132回中部日本整形外科災害外科学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 体軸性脊椎関節炎におけるTNFαの重要性2019

    • Author(s)
      冨田哲也
    • Organizer
      第92回日本整形外科学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 体軸性脊椎関節炎治療の最前線2019

    • Author(s)
      冨田哲也
    • Organizer
      第5回日本骨免疫学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 脊椎関節炎に対するIL-17Aワクチンの開発2019

    • Author(s)
      冨田哲也
    • Organizer
      第19回日本Men's Health医学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 日本におけるSpA診断の現状と課題2019

    • Author(s)
      冨田哲也、松原優里、中村好一
    • Organizer
      第29回日本脊椎関節炎学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Treatment Patterns Among Japanese Patients With Ankylosing Spondylitis(AS):Hospital Claims Database Analysis2019

    • Author(s)
      冨田哲也
    • Organizer
      第29回日本脊椎関節炎学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脊椎関節炎に対するIL/23阻害薬2019

    • Author(s)
      冨田哲也
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 本邦における体軸性脊椎関節炎の診断の現状と課題2019

    • Author(s)
      冨田哲也
    • Organizer
      第30回日本リウマチ学会 中国・四国支部学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Confirmation of HLA-B27 Transgenic Rats as a spondyloarthritis model2018

    • Author(s)
      Tetsuya Tomita, Hiroki Hayashi, Sun Jiao, Hironori Nakagami
    • Organizer
      26th annual meeting European Orthopaedic Reseach Society
    • Related Report
      2018 Research-status Report
  • [Book] 脊椎関節炎診療の手引き20202020

    • Author(s)
      冨田哲也
    • Total Pages
      150
    • Publisher
      診断と治療社
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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