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Fundamental research for the development of a novel anti-glycan antibody drug against multiple sclerosis

Research Project

Project/Area Number 20H03379
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionChiba University

Principal Investigator

KAWASHIMA Hiroto  千葉大学, 大学院薬学研究院, 教授 (50260336)

Co-Investigator(Kenkyū-buntansha) 小林 基弘  福井大学, 学術研究院医学系部門, 教授 (00362137)
安保 博仁  千葉大学, 大学院薬学研究院, 助教 (80868050)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsリンパ球ホーミング / 高内皮細静脈 / 抗糖鎖抗体 / 多発性硬化症 / 免疫疾患
Outline of Research at the Start

糖鎖は、分化・発生、免疫、癌化、タンパク質品質管理などにおいて様々な役割を果たし、近年、第三の生命鎖として注目されている。我々は、特定の糖鎖構造に特異的な抗糖鎖抗体を効率良く作製する方法論を開発し、親和性および特異性の高い様々な抗糖鎖抗体の作製に成功している。本研究では、新たに開発した抗糖鎖抗体による実験的自己免疫性脳脊髄炎の治療効果の検討を行い、糖鎖を標的とした新規免疫疾患治療薬の開発に向けた基盤を確立することを目指す。

Outline of Final Research Achievements

Glycans play various physiological roles in development, immunity, canceration, protein quality control, etc. Their functions as the third life chain and their potential as drug discovery targets have recently attracted attention. In this study, we used a newly developed anti-glycan antibody generated by our own methodology to examine its suppressing effects on experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. We obtained basic data for the development of novel antibody drugs against immune-related diseases.

Academic Significance and Societal Importance of the Research Achievements

免疫関連疾患の一種である多発性硬化症に関しては、治療薬が開発されているものの、それらには感染症や徐脈性不整脈等の副作用も知られており、作用機序の異なる新規治療薬の開発が望まれる。本研究では、独自に開発した糖鎖に結合する抗体が、多発性硬化症の新しい治療薬の候補となる可能性を検討し、有望な結果を得た。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (40 results)

All 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 7 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (3 results)

  • [Int'l Joint Research] Khoo K-H/台湾Academia Sinica(その他の国・地域(台湾))

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Kuo C-W/台湾Academia Sinica(その他の国・地域(台湾))

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Transcriptome Analysis of Tumor Vasculature Identifies Molecular Signature of Tumor-Associated High Endothelial Venules that Predicts Breast Cancer Survival.2022

    • Author(s)
      Sawada J, Hiraoka N, Qi R, Jiang L, Fournier-Goss AE, Yoshida M, Kawashima H, and Komatsu M.
    • Journal Title

      Cancer Immunol Res.

      Volume: 10 Issue: 4 Pages: 468-481

    • DOI

      10.1158/2326-6066.cir-21-0369

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Turkeys possess diverse Siaα2-3Gal glycans that facilitate their dual susceptibility to avian influenza viruses isolated from ducks and chickens.2022

    • Author(s)
      Kobayashi D, Hiono T, Ichii O, Nishihara S, Takase-Yoden S, Yamamoto K, Kawashima H, Isoda N, and Sakoda Y.
    • Journal Title

      Virus Res.

      Volume: 315 Pages: 198771-198771

    • DOI

      10.1016/j.virusres.2022.198771

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of crucial amino acid residues for antimicrobial activity of angiogenin 4 and its modulation of gut microbiota in mice.2022

    • Author(s)
      Sultana MF, Suzuki M, Yamasaki F, Kubota W, Takahashi K, Abo H and Kawashima H.
    • Journal Title

      Front. Microbiol.

      Volume: 13 Pages: 900948-900948

    • DOI

      10.3389/fmicb.2022.900948

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sulfated Glycans Recognized by S1 Monoclonal Antibody can Serve as a Diagnostic Marker for Malignant Pleural Mesothelioma2022

    • Author(s)
      Koki Nakashima, Yasuhiro Sakai, Hitomi Hoshino, Yukihiro Umeda, Hiroto Kawashima, Yoshitaka Sekido, Tamotsu Ishizuka, Motohiro Kobayashi
    • Journal Title

      Lung

      Volume: 200 Issue: 3 Pages: 531-534

    • DOI

      10.1007/s00408-022-00531-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan2022

    • Author(s)
      Umezawa F, Natsume M, Fukusada S, Nakajima K, Yamasaki F, Kawashima H, Kuo CW, Khoo KH, Shimura T, Yagi H, Kato K.
    • Journal Title

      Int J Mol Sci.

      Volume: 23 Issue: 12 Pages: 6662-6662

    • DOI

      10.3390/ijms23126662

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumor-associated neutrophils and macrophages exacerbate antidrug IgG-mediated anaphylactic reaction against an immune checkpoint inhibitor2022

    • Author(s)
      Arai Takahiro、Kokubo Tomomi、Tang Ruiheng、Abo Hirohito、Terui Ayu、Hirakawa Jotaro、Akita Hidetaka、Kawashima Hiroto、Hisaka Akihiro、Hatakeyama Hiroto
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 10 Issue: 12 Pages: e005657-e005657

    • DOI

      10.1136/jitc-2022-005657

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human and mouse angiogenins: Emerging insights and potential opportunities.2022

    • Author(s)
      Sultana MF, Abo H and Kawashima H.
    • Journal Title

      Front. Microbiol.

      Volume: 12 Pages: 1022945-1022945

    • DOI

      10.3389/fmicb.2022.1022945

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sulfated glycans containing NeuAcα2-3Gal facilitate the propagation of human H1N1 influenza A viruses in eggs.2021

    • Author(s)
      Ichimiya T, Okamatsu M, Kinoshita T, Kobayashi D, Ichii O, Yamamoto N, Sakoda Y, Kida H, Kawashima H, Yamamoto K, Takase-Yoden S, and Nishihara S
    • Journal Title

      Virology

      Volume: 562 Pages: 29-39

    • DOI

      10.1016/j.virol.2021.06.008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic effects of an anti-sialyl Lewis X antibody in a murine model of allergic asthma.2021

    • Author(s)
      Xiong W, Liu W, Nishida S, Komiyama D, Liu W, Hirakawa J and Kawashima H
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 22 Issue: 18 Pages: 9961-9961

    • DOI

      10.3390/ijms22189961

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a novel monoclonal antibody against truncated glycoforms of α-dystroglycan lacking matriglycans2021

    • Author(s)
      Yamasaki Fumiya、Umezawa Fumiko、Sensui Tomohiro、Anzo Masashi、Abo Hirohito、Kuo Chu-Wei、Khoo Kay-Hooi、Kato Koichi、Yagi Hirokazu、Kawashima Hiroto
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 579 Pages: 8-14

    • DOI

      10.1016/j.bbrc.2021.09.043

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ribosome Profiling in Streptococcus pneumoniae Reveals the Role of Methylation of 23S rRNA Nucleotide G748 on Ribosome Stalling2021

    • Author(s)
      Tatsuma Shoji、Akiko Takaya、Yoko Kusuya、Hiroki Takahashi、Hiroto Kawashima
    • Journal Title

      Journal of Genetics & Genomic Sciences

      Volume: 6 Issue: 1 Pages: 1-16

    • DOI

      10.24966/ggs-2485/100024

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A molecular map of murine lymph node blood vascular endothelium at single cell resolution2020

    • Author(s)
      Brulois Kevin、Rajaraman Anusha、Szade Agata、Nordling Sofia、Bogoslowski Ania、Dermadi Denis、Rahman Milladur、Kiefel Helena、O’Hara Edward、Koning Jasper J.、Kawashima Hiroto、Zhou Bin、Vestweber Dietmar、Red-Horse Kristy、Mebius Reina E.、Adams Ralf H.、Kubes Paul、Pan Junliang、Butcher Eugene C.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41467-020-17291-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] マウスB細胞の組織環境依存的なシアリルルイスX発現機構の解明2022

    • Author(s)
      鈴木太朗、込山大智、竹添智宏、松村龍志、関根成隆、西田匠吾、平川城太朗、川島博人
    • Organizer
      2022年度日本生化学会関東支部例会
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウスB細胞における糖鎖抗原シアリルルイスXの発現機構の解明2022

    • Author(s)
      鈴木太朗、込山大智、竹添智宏、松村龍志、関根成隆、西田匠吾、平川城太朗、川島博人
    • Organizer
      第22回 Pharmaco-Hematology シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 制御性T細胞表面シアリルルイスX糖鎖抗原の炎症における役割の解明2022

    • Author(s)
      大石かなえ、西田匠吾、石倉晨規、安保博仁、中司寛子、川島博人
    • Organizer
      第21回ファーマ・バイオフォーラム
    • Related Report
      2022 Annual Research Report
  • [Presentation] Expression and function of sialyl Lewis X glycans on mouse regulatoly T cells.2022

    • Author(s)
      Kanae Ohishi, Shogo Nshida, Asaki Ishikura, Hirohito Abo, Hiroto Kawashima
    • Organizer
      Sialoglyco 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of a novel anti-glycan monoclonal antibody applicable for the treatment of immune-related diseases.2022

    • Author(s)
      Hiroto Kawashima
    • Organizer
      SLDDDRS Webinar Series 2021-2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Expression and function of sialyl Lewis X glycans on mouse regulatoly T cells2022

    • Author(s)
      Kanae Ohishi, Shogo Nshida, Asaki Ishikura, Hirohito Abo, Hiroko Nakatsukasa, Hiroto Kawashima
    • Organizer
      第51回日本免疫学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗糖鎖抗体を用いた間質-細胞相互作用の解析2021

    • Author(s)
      川島博人
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] リンパ球ホーミングと糖鎖2021

    • Author(s)
      川島博人
    • Organizer
      第1回Glycotext講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ムチン硫酸化による生体防御2021

    • Author(s)
      安保博仁、川島博人
    • Organizer
      日本薬学会関東支部会第14回若手シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Therapeutic effects of anti-sialyl Lewis X antibody in a murine model of allergic asthma.2021

    • Author(s)
      Wei Xiong, Shogo Nishida, Jotaro Hirakawa, Hiroto Kawashima
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マトリグリカン欠損ジストログリカンに対する新規モノクローナル抗体の樹立2021

    • Author(s)
      山崎郁弥、梅澤芙美子、安藏匡史、安保博仁、加藤晃一、矢木宏和、川島博人
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 真核生物のグリセロールリン酸修飾に必要なCDP-グリセロールを合成する酵素の同定2021

    • Author(s)
      梅澤芙美子、矢木宏和、山崎郁弥、志村貴也、中嶋和紀、川島博人、加藤晃一
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒトHlNlインフルエンザAウイルスは発育鶏卵の羊膜・尿膜に発現するα2,3結合シアル酸を含む硫酸化糖鎖分子をレセプターとして利用する2021

    • Author(s)
      高瀬明、一宮智美、 岡松正敏、木下貴明、小林大樹、市居修、山本直樹、迫田義博、喜田宏、 川島博人、山本一夫、西原祥子
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 制御性T細胞表面シアリルルイスX糖鎖抗原の炎症における役割2021

    • Author(s)
      大石かなえ、西田匠吾、石倉晨規、安保博仁、川島博人
    • Organizer
      第21回 Pharmaco-Hematology シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] マウスB細胞における糖鎖抗原シアリルルイスXの発現機構の解明2021

    • Author(s)
      込山大智、竹添智宏、関根成隆、西田匠吾、川島博人
    • Organizer
      第21回 Pharmaco-Hematology シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] シアリルルイスX糖鎖抗原を発現する制御性T細胞の体内動態と機能2021

    • Author(s)
      大石かなえ、西田匠吾、石倉晨規、安保博仁、川島博人
    • Organizer
      GlycoTOKYO2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 制御性T細胞表面シアリルルイスX糖鎖抗原の炎症に伴う発現変化2020

    • Author(s)
      西田匠吾、竹添知宏、関根成隆、込山大智、安保博仁、川島博人
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] オートファジーと硫酸化ムチンによる大腸炎防御2020

    • Author(s)
      川島博人
    • Organizer
      第64回日本薬学会関東支部大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マウスB細胞におけるフコシル化糖鎖抗原シアリルルイスXの発現解析2020

    • Author(s)
      込山 大智、竹添 智宏、松村 龍志、関根 成隆、西田 匠吾、平川 城太朗、川島 博人
    • Organizer
      第39回日本糖質学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 制御性T細胞表面シアリルルイスX糖鎖抗原の炎症に伴う発現変化と機能の解析2020

    • Author(s)
      西田匠吾、竹添知宏、関根成隆、込山大智、安保博仁、川島博人
    • Organizer
      第39回日本糖質学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抗糖鎖抗体のマウス気管支喘息治療効果の検討2020

    • Author(s)
      熊偉、Liu wenxin、劉偉、平川城太朗、川島博人
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] LPS誘発性急性肺損傷における抗シアリルルイスX糖鎖抗体の治療効果の解析2020

    • Author(s)
      Liu Wenxin、熊 偉、 安保 博仁、 川島 博人
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウスB細胞における糖鎖抗原シアリルルイスXの発現機構の解明2020

    • Author(s)
      込山 大智、竹添 智宏、松村 龍志、関根 成隆、西田 匠吾、平川 城太朗、川島 博人
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院・免疫微生物学研究室

    • Related Report
      2022 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院・免疫微生物学研究室

    • URL

      https://www.p.chiba-u.jp/lab/bisei/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院 免疫微生物学研究室

    • URL

      https://www.p.chiba-u.jp/lab/bisei/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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