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An immunotherapy model for hematopoietic malignancies (multiple myeloma) using humanized mice

Research Project

Project/Area Number 17K07142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory animal science
Research InstitutionHyogo Medical University

Principal Investigator

Yoshihara Satoshi  兵庫医科大学, 医学部, 講師 (90461037)

Co-Investigator(Kenkyū-buntansha) 岡田 昌也  兵庫医科大学, 医学部, 講師 (00309452)
相馬 俊裕  兵庫医科大学, 医学部, 非常勤講師 (40273619)
吉原 享子  兵庫医科大学, 医学部, 助教 (80595265)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords多発性骨髄腫 / 間葉系幹細胞 / 間葉系細胞 / ヒト化マウス / 免疫療法
Outline of Final Research Achievements

Myeloma cells from multiple myeloma patients were tested for three-dimensional culture using an extracellular matrix. In addition, a platform to create an immunotherapy model using peripheral blood stem cells from the same case as the myeloma cells was developed. We also analyzed the profile of aberrant antigen expression in plasma cells using clinical specimens from MGUS, symptomatic myeloma, and other related diseases. Moreover, we examined the feasibility of intensified induction therapy in newly diagnosed myeloma patients, consisted by 6 cycles of bortezomib, lenalidomide, and dexamethasone and reported the promising results.

Academic Significance and Societal Importance of the Research Achievements

血液がんの治療は急速に進歩してきており、多発性骨髄腫の予後も急速に改善しているが、未だに治癒が得られる病気ではない。今後の治療開発のため、骨髄腫患者自身の腫瘍細胞と造血幹細胞を用いた疾患および治療モデルの作成を試みている。また、より臨床面に近いところでは、自家移植の適応となる多発性骨髄腫患者に対する治療開発として、ボルテゾミブ、レナリドミド、デキサメタゾンの3剤併用レジメンを6コース行ってから造血幹細胞を採取し、さらに大量化学療法+自家末梢血幹細胞移植を施行するという導入療法を強化した治療レジメンの有用性を示した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (23 results)

All 2020 2019 2018 2017

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (14 results)

  • [Journal Article] Treatment strategy in a patient showing borderline features between plasmablastic lymphoma and plasmablastic myeloma harboring a 17p deletion2020

    • Author(s)
      Yoshihara Kyoko、Yoshihara Satoshi、Matsuda Ikuo、Imado Takehito、Matsuo Shohei、Okada Masaya、Shimizu Yoshifumi、Hirota Seiichi、Fujimori Yoshihiro
    • Journal Title

      Annals of Hematology

      Volume: 99 Issue: 6 Pages: 1405-1407

    • DOI

      10.1007/s00277-020-03975-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial2019

    • Author(s)
      Yamahara K、Hamada A、Soma T、Okamoto R、Okada M、Yoshihara S、Yoshihara K、Ikegame K、Tamaki H、Kaida K、Inoue T、Ohsugi Y、Nishikawa H、Hayashi H、Ito Y、Iijima H、Ohnishi S、Hashimoto D、Isoe T、Teshima T、Ogawa H、Sato N、Fujimori Y
    • Journal Title

      BMJ Open

      Volume: 9 Issue: 7 Pages: e026403-e026403

    • DOI

      10.1136/bmjopen-2018-026403

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low incidence of HHV‐6 reactivation in haploidentical hematopoietic stem cell transplantation with corticosteroid as graft‐vs‐host disease prophylaxis compared with cord blood transplantation2019

    • Author(s)
      Tamaki Hiroya、Ikegame Kazuhiro、Yoshihara Satoshi、Kaida Katsuji、Yoshihara Kyoko、Inoue Takayuki、Kato Ruri、Nakata Jun、Fujioka Tatsuya、Soma Toshihiro、Okada Masaya、Ogawa Hiroyasu
    • Journal Title

      Transplant Infectious Disease

      Volume: - Issue: 3

    • DOI

      10.1111/tid.13073

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictive value of interim FDG-PET/CT findings in patients with diffuse large B-cell lymphoma treated with R-CHOP2019

    • Author(s)
      Kitajima Kazuhiro、Okada Masaya、Yoshihara Kyoko、Tokugawa Tazuko、Sawada Akihiro、Yoshihara Satoshi、Tamaki Hiroya、Fujimori Yoshihiro、Ueda Syuji、Kawamoto Hiroyuki、Taniguchi Junichi、Yamakado Koichiro
    • Journal Title

      Oncotarget

      Volume: 10 Issue: 52 Pages: 5403-5411

    • DOI

      10.18632/oncotarget.27103

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early evaluation of tumor response to 90Y-ibritumomab radioimmunotherapy in relapsed/refractory B cell non-Hodgkin lymphoma: what is the optimal timing for FDG-PET/CT?2019

    • Author(s)
      Kitajima K, Okada M, et al.
    • Journal Title

      Eur Radiol.

      Volume: - Issue: 7 Pages: 3935-3944

    • DOI

      10.1007/s00330-019-06134-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Posttransplant Hemophagocytic Lymphohistiocytosis Driven by Myeloid Cytokines and Vicious Cycles of T-Cell and Macrophage Activation in Humanized Mice2019

    • Author(s)
      Yoshihara Satoshi、Li Yuying、Xia Jinxing、Danzl Nichole、Sykes Megan、Yang Yong-Guang
    • Journal Title

      Frontiers in Immunology

      Volume: 10

    • DOI

      10.3389/fimmu.2019.00186

    • Related Report
      2018 Research-status Report
  • [Journal Article] Aldehyde dehydrogenase activity in cryopreserved cord blood cells for quality assessment prior to transplantation2018

    • Author(s)
      Ikemoto Junko、Yoshihara Satoshi、Kobayashi Tamami、Kai Shunro、Fujimori Yoshihiro
    • Journal Title

      Molecular Medicine Reports

      Volume: 18 Pages: 4530-4534

    • DOI

      10.3892/mmr.2018.9481

    • Related Report
      2018 Research-status Report
  • [Journal Article] A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced-intensity conditioning.2018

    • Author(s)
      Okada M, Tasaka T, et al.
    • Journal Title

      Eur J Haematol.

      Volume: 100 Issue: 4 Pages: 335-343

    • DOI

      10.1111/ejh.12999

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment2018

    • Author(s)
      Okada M, Imagawa J, et al.
    • Journal Title

      Clin Lymphoma Myeloma Leuk.

      Volume: 18 Issue: 5 Pages: 353-360

    • DOI

      10.1016/j.clml.2018.03.004

    • NAID

      120006463738

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Feasibility of 6 cycles of VRd/KRd as induction therapy prior to stem-cell collection in transplant-eligible multiple myeloma.2020

    • Author(s)
      Yoshihara Kyoko, Shimizu Yoshifumi, Yoshihara Satoshi, Takatsuka Hiroyuki, Kawamoto Hiroyuki, Imado Takehito, Okada Masaya, Fujimori Yoshihiro
    • Organizer
      第42回造血細胞移植学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DLBCL再発例の治療および予後に関する後方視的解析2019

    • Author(s)
      吉原享子, 清水義文, 高塚広行, 川本裕之, 吉原哲, 徳川多津子, 澤田暁宏, 玉置広哉, 岡田昌也, 三澤眞人, 伊福秀貴, 大江与喜子, 藤盛好啓.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Ph陽性ALL患者における移植後TKI維持療法の有用性2019

    • Author(s)
      福永景子, 池亀和博, 海田勝仁, 井上貴之, 吉原哲, 吉原享子, 大杉夕子, 玉置広哉, 岡田昌也, 小川啓恭, 藤盛好啓
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 生物由来原料基準を満たす国産ウシ血小板溶解物「NeoSERA」を原材料とする羊膜由来間葉系幹細胞の細胞製剤化2019

    • Author(s)
      山原研一, 浜田彰子, 黒田将子, 池本純子, 吉原享子, 吉原哲, 岡田昌也, 橋本大吾, 相馬俊裕, 豊嶋崇徳, 藤盛好啓
    • Organizer
      第67回日本輸血・細胞治療学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Detailed bone marrow plasma cell phenotyping in the patients with suspected plasma cell disorders.2018

    • Author(s)
      Yoshihara Satoshi, Yoshihara Kyoko, Ikemoto Junko, Onomoto Hitomi, Sugiyama Hiroki, Ikegame Kazuhiro, Tamaki Hiroya, Okada Masaya, Osugi Yuko, Fujimori Yoshihiro
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Bendamustine plus rituximab in the treatment of indolentlymphoma.2018

    • Author(s)
      Yoshihara Kyoko, Shimizu Yoshifumi, Kawamoto Hiroyuki, Takatsuka Hiroyuki, Tokugawa Tazuko, Sawada Akihiro, Yoshihara Satoshi, Okada Masaya, Misawa Mahito, Ifuku Hidetaka, Okamoto Takahiro, Ooe Yokiko, Fujimori Yoshihiro
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] V-EPOCHが著効したdel 17pを有するplasmablastic lymphoma/myelomaの1例2018

    • Author(s)
      吉原享子, 吉原哲, 松田育雄, 松尾祥平, 今戸健人, 岡田昌也, 廣田誠, 藤盛好啓
    • Organizer
      第43回日本骨髄腫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] IgA型M蛋白の急激な上昇を伴う骨髄再発を来した胸腺MALTリンパ腫の一例2018

    • Author(s)
      吉原哲 , 松田育雄, 吉原享子, 池本純子, 岡山昌也, 廣田誠一, 藤盛好啓
    • Organizer
      第58回日本リンパ網内系学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Len/dexによる導入療法後に大量メルファラン療法+自家末梢血幹細胞移植を施行したPOEMS症候群の一例2018

    • Author(s)
      円山牧子, 吉原享子, 松田育雄, 吉原哲, 岡田昌也, 廣田誠一, 藤盛好啓
    • Organizer
      第58回日本リンパ網内系学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] V-EPOCHが著効したdel 17pを有するplasmablastic lymphoma/myelomaの1例2018

    • Author(s)
      吉原享子、吉原哲、松田育雄、松尾祥平、今戸健一、岡田昌也、廣田誠一、藤盛好啓
    • Organizer
      第43回日本骨髄腫学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当院におけるテムセルHS注の運用2018

    • Author(s)
      池本純子、杉山寛貴、原田由紀、大塚真哉、小野本仁美、入江玲子、 奥田典子、村田理恵、前田和宏、吉原享子、吉原哲、岡田昌也、 山原研一、相馬俊裕、藤盛好啓
    • Organizer
      第40回日本造血細胞移植学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 非寛解白血病に対するハプロミニ移植におけるWT1測定の意義:単施設解析2018

    • Author(s)
      玉置広哉、池亀和博、海田勝仁、丸山聡、眞弓あずさ、井上貴之、 寺本昌弘、吉原哲、岡田昌也、小川啓恭
    • Organizer
      第40回日本造血細胞移植学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Frailty score-based treatment strategy for transplant-ineligible elderly myeloma patients2017

    • Author(s)
      吉原享子、吉原哲、池本純子、岡田昌也、山原研一、相馬俊裕、藤盛好啓
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当院におけるテムセルHS注の管理体制の構築2017

    • Author(s)
      杉山 寛貴, 原田 由紀, 大塚 真哉, 小野本 仁美, 入江 玲子, 奥田 典子, 村田 理恵, 前田 和宏, 池本 純子, 吉原 享子, 吉原 哲, 山原 研一, 相馬 俊裕, 藤盛 好啓
    • Organizer
      第65回日本輸血・細胞治療学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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