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Development of a novel lymphoma PDX model using humanized mice

Research Project

Project/Area Number 20K21547
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionKobe University

Principal Investigator

Saito Yasuyuki  神戸大学, 医学研究科, 講師 (40508842)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsPDXモデル / ヒト化マウス / がん微小環境 / マクロファージ / CD47 / SIRPα
Outline of Research at the Start

本研究は、研究代表者が独自のノウハウを有している免疫細胞ヒト化マウスを用いた腫瘍モデルの実験系による、マクロファージ、樹状細胞などのヒト骨髄系細胞の機能の再現によるがん微小環境の構築、ならびに患者由来腫瘍(PDX)モデルにおける患者由来がん微小環境の構築と新たな治療標的の探索を目的とし研究を進めていく。本研究成果により、これまで再現が困難であったがん微小環境におけるヒト免疫細胞のin vivoでの評価が可能となり、がん微小環境のさらなる理解に貢献することが期待される。さらに本研究成果は、リンパ腫の病因の理解やマクロファージ、樹状細胞を標的とした新たな診断や治療法の確立に繋がる可能性を有する。

Outline of Final Research Achievements

In this research, we created an experimental system by transplanting human B lymphoma patient-derived tumor cells into immune-cell humanized mice (immunodeficient mice transplanted with CD34-positive cells isolated from human cord blood cells) to establish a lymphoma patient-derived xenograft (PDX) model and to validate the efficacy of anti-human SIRPα antibody in vivo. We found the infiltration of human macrophages in the tumors and the antitumor effect of rituximab and anti-human SIRPα antibody using this model. Thus, our findings indicate that this model can be a new tool for evaluating cancer immunotherapy, particularly targeting human macrophages in vivo.

Academic Significance and Societal Importance of the Research Achievements

研究代表者が開発した「免疫細胞ヒト化マウスを用いた患者由来がん異種移植(PDX)モデル」を用いることによって、リンパ腫の病因の理解やマクロファージを標的とした新たな診断や治療法の確立に繋がる可能性を有している。さらに、研究代表者らが見出した膜型分子SIRPαを標的としたがん免疫療法の有効性を検証する前臨床モデルとして有用であることが示されたことから、本研究によって学術的成果と共に、新規がん治療法の創出に資する社会的意義の高い研究成果を得られた。

Report

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

    (14 results)

All 2021 2020 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Editorial: Advances in Human Immune System Mouse Models for Studying Human Hematopoiesis and Cancer Immunotherapy2021

    • Author(s)
      Saito Yasuyuki、Willinger Tim、Theocharides Alexandre P. A.
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 829644-829644

    • DOI

      10.3389/fimmu.2021.829644

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anticancer efficacy of monotherapy with antibodies to SIRPα/SIRPβ1 mediated by induction of antitumorigenic macrophages2021

    • Author(s)
      Sakamoto Mariko、Murata Yoji、Tanaka Daisuke、Kakuchi Yuka、Okamoto Takeshi、Hazama Daisuke、Saito Yasuyuki、Kotani Takenori、Ohnishi Hiroshi、Miyasaka Masayuki、Fujisawa Masato、Matozaki Takashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 1

    • DOI

      10.1073/pnas.2109923118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BRAFV600E or mutant MAP2K1 human CD34+ cells establish Langerhans cell?like histiocytosis in immune-deficient mice2020

    • Author(s)
      Rafiei Anahita、Wilk C. Matthias、Helbling Patrick M.、Myburgh Renier、Saito Yasuyuki、Haralambieva Eugenia、Soldini Davide、Chakraborty Rikhia、Merad Miriam、Allen Carl E.、Nombela-Arrieta Cesar、Manz Markus G.
    • Journal Title

      Blood Advances

      Volume: 4 Issue: 19 Pages: 4912-4917

    • DOI

      10.1182/bloodadvances.2020001926

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blockade of CD47 or SIRPα: a new cancer immunotherapy2020

    • Author(s)
      Murata Yoji、Saito Yasuyuki、Kotani Takenori、Matozaki Takashi
    • Journal Title

      Expert Opinion on Therapeutic Targets

      Volume: 24 Issue: 10 Pages: 945-951

    • DOI

      10.1080/14728222.2020.1811855

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrocyclic Peptide-Mediated Blockade of the CD47-SIRPα Interaction as a Potential Cancer Immunotherapy2020

    • Author(s)
      Hazama Daisuke、Yin Yizhen、Murata Yoji、Matsuda Makoto、Okamoto Takeshi、Tanaka Daisuke、Terasaka Naohiro、Zhao Jinxuan、Sakamoto Mariko、Kakuchi Yuka、Saito Yasuyuki、Kotani Takenori、Nishimura Yoshihiro、Nakagawa Atsushi、Suga Hiroaki、Matozaki Takashi
    • Journal Title

      Cell Chemical Biology

      Volume: 27 Issue: 9 Pages: 1181-1191.e7

    • DOI

      10.1016/j.chembiol.2020.06.008

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIRPα on Mouse B1 Cells Restricts Lymphoid Tissue Migration and Natural Antibody Production2020

    • Author(s)
      Franke Katka、Pillai Saravanan、Hoogenboezem Mark、Gijbels Marion、Matlung Hanke、Geissler Judy、Olsman Hugo、Pottgens Chantal、van Gorp Patrick、Ozsvar-Kozma Maria、Saito Yasuyuki、Matozaki Takashi、Kuijpers Taco、Hendriks Rudi、Kraal Georg、Binder Christoph、de Winther Menno、van den Berg Timo
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 570963-570963

    • DOI

      10.3389/fimmu.2020.570963

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis2020

    • Author(s)
      Nishimura Taichi、Saito Yasuyuki、Washio Ken、Komori Satomi、Respatika Datu、Kotani Takenori、Murata Yoji、Ohnishi Hiroshi、Mizobuchi Satoshi、Matozaki Takashi
    • Journal Title

      European Journal of Immunology

      Volume: 50 Issue: 10 Pages: 1560-1570

    • DOI

      10.1002/eji.201948410

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tetrameric glycoprotein complex gH/gL/gQ1/gQ2 is a promising vaccine candidate for human herpesvirus 6B2020

    • Author(s)
      Wang Bochao、Hara Kouichi、Kawabata Akiko、Nishimura Mitsuhiro、Wakata Aika、Tjan Lidya Handayani、Poetranto Anna Lystia、Yamamoto Chisato、Haseda Yasunari、Aoshi Taiki、Munakata Lisa、Suzuki Ryo、Komatsu Masato、Tsukamoto Ryuko、Itoh Tomoo、Nishigori Chikako、Saito Yasuyuki、Matozaki Takashi、Mori Yasuko
    • Journal Title

      PLOS Pathogens

      Volume: 16 Issue: 7 Pages: e1008609-e1008609

    • DOI

      10.1371/journal.ppat.1008609

    • NAID

      120006940234

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A novel humanized mouse model in vivo evaluation of cancer immunotherapy targeting human macrophages2021

    • Author(s)
      Yasuyuki Saito, Rie Iida, Daisuke Hazama, Takenori Kotani, Yoji Murata, Hiroshi Yokozaki, Takashi Matozaki
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Preclinical Evaluation of the efficacy of anti-human SIRPα antibody for cancer immunotherapy by the use of humanized mice2021

    • Author(s)
      Yasuyuki Saito, Rie Iida-Norita, Daisuke Hazama, Refaat Alaa, Satomi Komori, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] A novel humanized mouse model for assessing human macrophage-targeted cancer immunotherapy in vivo2021

    • Author(s)
      Rie Iida-Norita, Yasuyuki Saito, Daisuke Hazama, Satomi Komori, Hiroki Yoshida, Risa Sugihara, Yoji Murata, and Takashi Matozaki
    • Organizer
      神戸大学・理研BDR合同シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] Humanized mouse models for in vivo evaluation of cancer immunotherapy targeting human macrophages2020

    • Author(s)
      Yasuyuki Saito, Rie Iida, Daisuke Hazama, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] A novel humanized mouse model for assessing human macrophage-targeted cancer immunotherapy in vivo2020

    • Author(s)
      Rie Iida-Norita, Yasuyuki Saito, Daisuke Hazama, Satomi Komori, Hiroki Yoshida, Risa Sugihara, Yoji Murata, and Takashi Matozaki
    • Organizer
      14th International Conference on Protein Phosphatase
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Remarks] 研究室ホームページ

    • URL

      https://www.med.kobe-u.ac.jp/tougou/signal/Home.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2023-01-30  

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