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Establishment of therapeutic mAbs for malignant lymphoma

Research Project

Project/Area Number 15K06880
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionJuntendo University

Principal Investigator

MATSUOKA Shuji  順天堂大学, 医学部, 助教 (20286743)

Co-Investigator(Kenkyū-buntansha) 小松 則夫  順天堂大学, 医学部, 教授 (50186798)
Research Collaborator ABE Masaaki  順天堂大学, 医学部, 技師
TOYOTA Tokuko  順天堂大学, 医学部, 協力研究員
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアナポコーシス / 治療 / モノクローナル抗体 / 細胞死 / 汎HLA- class II / 細胞骨格 / 悪性リンパ腫 / 成人T細胞白血病 / Anapocosis / monoclonal antibody / therapy / cell death / lymphoma / Adult T cell Leukemia / humanized m Ab / 悪性リンパ腫治療抗体 / NKリンフォーマ / アポトーシス / 抗体治療薬 / MHC classs II / Death Receptor
Outline of Final Research Achievements

To develop a new therapeutic monoclonal Antibody (mAb) for Hodgkin lymphoma (HL), we immunized a mouse with live HL cell lines, After hybridization, we screened the hybridoma clones by assessing direct cytotoxicity against a HL cell line not used for immunization. A newly established mouse anti-human mAb (4713) triggered cytoskeleton-dependent, but complement- and caspase-independent, cell death in HL cell lines, Burkitt lymphoma cell lines, and advanced adult T-cell leukemia cell lines. mAb 4713 was revealed to be a mouse anti- human pan-HLA class II mAb. Treatment with this mAb induced the formation of large pores on the surface of target lymphoma cells within 30 min. This finding suggests that the cell death process induced by this anti-pan HLA-class II mAb may involve the same death signals stimulated by a cytolytic anti-pan MHC class I mAb that also induces large pore formation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (28 results)

All 2017 2016 2015 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (8 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 3 results)

  • [Journal Article] 2.Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.2016

    • Author(s)
      Matsuoka S, Ishii Y, Nakao A, Abe M, Ohtsuji N, Momose S, Jin H, Arase H, Sugimoto K, Nakauchi Y, Masutani H, Maeda M, Yagita H, Komatsu N, Hino O.
    • Journal Title

      PLoS One.

      Volume: 11(3)

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Establishment of anti-mesothelioma monoclonal antibodies.2016

    • Author(s)
      Mizutani N, Abe M, Matsuoka S, Kajino K, Wakiya M, Ohtsuji N, Hatano R, Morimoto C, Hino O.
    • Journal Title

      BMC Res Notes.

      Volume: 9 Pages: 324-324

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.2016

    • Author(s)
      Matsuoka S, Ishii Y, Nakao A, Abe M, Ohtsuji N, Momose S, Jin H, Arase H, Sugimoto K, Nakauchi Y, Masutani H, Maeda M, Yagita H, Komatsu N, Hino O.
    • Journal Title

      PLoS One.

      Volume: 11(3)

    • NAID

      120005838168

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Anapocosis: Direct cell death lymphoma cells induced by mAbs2017

    • Author(s)
      Shuji Matsuoka, Hideo Yagita, Koichiro Uchida
    • Organizer
      日本免疫学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cell death of activated lymphocytes and lymphoma/leukemia cells induced by MHC class I and II mAbs (Anapocosis)2017

    • Author(s)
      松岡周二
    • Organizer
      日本癌学会(第76回日本癌学会学術総会シンポジウム)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 悪性リンパ腫細胞やATL細胞をアナポコーシス(Anapocosis)によって破壊する治療抗体2017

    • Author(s)
      松岡周二
    • Organizer
      日本がん分子標的治療学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Non Apoptotic,Non Necrotic Novel Cell Death (Anapocosis) of Lymphoma Cells Induced by Therapeutic mAb2016

    • Author(s)
      松岡周二
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Non Apoptotic, Non necrotic Novel Cell Death of Lymphoma Cells Induced by Therapeutic Mobs2016

    • Author(s)
      Shuji Matsuoka
    • Organizer
      BIT’s 7th World Gene Convention-2016 Shanghai, China 2016 November
    • Place of Presentation
      Sheraton Shanghai Waigaoqiao Hotel, China
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] アナポコーシス(ある種の抗体は腫瘍細胞に巨大な穴をあけて補体やカスペース非依存性に殺す)2016

    • Author(s)
      松岡周二
    • Organizer
      第25回日本Cell Death 学会
    • Place of Presentation
      品川区立総合区民会館
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Establishment of a therapeutic anti-pan HLA-class II monoclonal antibody that directly induces lymphoma cell death via large pore formation.2016

    • Author(s)
      Shuji Matsuoka
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Melbourne Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cell death of activated lymphocytes and lymphoma/leukemia cells induced by MHC class I and class II mAbs2016

    • Author(s)
      松岡周二 水谷奈津子
    • Organizer
      動物モデル研究の新たな可能性
    • Place of Presentation
      琵琶湖ホテル( 滋賀県 大津市)
    • Year and Date
      2016-02-04
    • Related Report
      2015 Research-status Report
  • [Presentation] 悪性中皮腫に対する新規抗体作製2016

    • Author(s)
      水谷奈津子 松岡周二 阿部雅明 梶野一徳 脇屋緑 大辻奈穂美、森本幾夫、樋野興夫
    • Organizer
      動物モデル研究の新たな可能性
    • Place of Presentation
      琵琶湖ホテル( 滋賀県 大津市)
    • Year and Date
      2016-02-04
    • Related Report
      2015 Research-status Report
  • [Presentation] 抗汎HLA class II抗体はリンパ腫細胞、ATL細胞、患者DLBCL細胞をアナポコーシスで殺す。2016

    • Author(s)
      松岡周二
    • Organizer
      第23回福岡血液研究会 2016年11月
    • Place of Presentation
      タカクラホテル福岡8階「真珠」
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 抗汎MHC モノクローナル抗体はリンパ腫やATL,の細胞株だけでなく、患者の白血化したリンパ腫細胞もアナポコーシスで殺した2016

    • Author(s)
      松岡周二
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2016 Research-status Report
  • [Presentation] Cytolytic anti-pan HLA class II mAb and anti-MHC class I mAb directly induce lymphoma cell death via large pore formation2015

    • Author(s)
      MATSUOKA Shuji, YAGITA Hideo, ISHII Yasuyuki
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      Sapporo Convention Center ( 北海道 札幌市)
    • Year and Date
      2015-11-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Anti-pan MHC class I and class II mAbs directly induce lymphoma cell death via large pore formation2015

    • Author(s)
      Shuji Matsuoka, Natsuko Mizutani, Hisashi Arase, Okio Hino
    • Organizer
      第74回日本癌学会
    • Place of Presentation
      名古屋国際会議場( 愛知県 名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Establishment of new therapeutic Abs for Malignant Mesothelioma2015

    • Author(s)
      Natsuko Mizutani, Shuji MATSUOKA, Kazunori KAJINO, Midori WAKIYA, Okio HINO
    • Organizer
      第74回日本癌学会
    • Place of Presentation
      名古屋国際会議場( 愛知県 名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Remarks] 新規の作用機序による悪性リンパ腫治療抗体の樹立~がん細胞に大きな穴をあけて破壊する~

    • URL

      http://www.juntendo.ac.jp/albums/abm.php?f=abm00015320.pdf&n=NewsRelease+20160406.pdf

    • Related Report
      2016 Research-status Report
  • [Remarks] 順天堂大、血液がん細胞に穴をあけて死滅させる抗体を樹立

    • URL

      http://news.mynavi.jp/news/2016/04/07/092/

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Remarks] 新規の作用機序による悪性リンパ腫治療抗体の樹立 がん細胞に大きな穴をあけて破壊(アナポコーシス)

    • URL

      http://science-soku.blog.jp/archives/57959773.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 順天堂大、血液がん細胞に穴をあけて死滅させる抗体を樹立

    • URL

      http://news.livedoor.com/article/detail/11386379/

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Remarks] VCが主導で設立の日本抗体医薬、ホジキンリンパ腫治療薬の開発目指す

    • URL

      https://bio.nikkeibp.co.jp/atcl/column/16/021500017/040600027/

    • Related Report
      2016 Research-status Report
  • [Remarks] 新規の作用機序による悪性リンパ腫治療抗体の樹立~がん細胞に大きな穴をあけて破壊する~

    • URL

      http://www.juntendo.ac.jp/news/20160406-01.html

    • Related Report
      2015 Research-status Report
  • [Remarks] がん細胞に大きな穴をあけて破壊、新規作用機序の悪性リンパ腫治療抗体を樹立-順大

    • URL

      http://www.qlifepro.com/news/20160408/malignant-lymphoma-therapeutic-antibodies-of-the-new-mechanism-of-action.html

    • Related Report
      2015 Research-status Report
  • [Remarks] 新規の作用機序による悪性リンパ腫治療抗体の樹立 がん細胞に大きな穴をあけて破壊する

    • URL

      http://science-soku.blog.jp/archives/2016-04-07.html

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 抗CD10抗体2017

    • Inventor(s)
      水谷奈津子、安倍雅明、松岡周二
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Therapeutic Agent for Malignant Tumors Expressing MHC class II2015

    • Inventor(s)
      松岡周二、石井保之
    • Industrial Property Rights Holder
      順天堂大学, 理化学研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-04-05
    • Acquisition Date
      2016-04-05
    • Related Report
      2016 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] THERAPEUTIC AGENT FOR MALIGNANT TUMORS EXPRESSING MHC CLASS II2015

    • Inventor(s)
      Shuji Matsuoka, Yasuyuki Ishii
    • Industrial Property Rights Holder
      順天堂大学, 理化学研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-04-01
    • Acquisition Date
      2016-02-19
    • Related Report
      2015 Research-status Report
    • Overseas

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Published: 2015-04-16   Modified: 2019-03-29  

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