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Development of innovative antitumor drugs that strongly induce phagocytosis of cancer cells by macrophages

Research Project

Project/Area Number 22K19458
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

Matozaki Takashi  神戸大学, 医学研究科, 特命教授 (80252782)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords抗体医薬 / 抗体依存性細胞貪食 / マクロファージ / SIRPα / CD47
Outline of Research at the Start

本研究では、CD47-SIRPα系を阻害した条件下で、がん細胞に発現する分子に対する抗体の機能スクリーング系を新たに確立し、様々な種類のがんに関して、マクロファージの腫瘍に対する抗体依存性貪食活性を強力に誘導でき優れた抗腫瘍効果を示す新規の治療薬を開発する。さらに、CD47-SIRPα系とは独立した、マクロファージによるがん細胞の貪食を抑制する新たな制御系を見出し、その系を利用した新規のがん治療法の開発をする。

Outline of Final Research Achievements

CD47, a membrane molecule expressed on cancer cells, forms the intercellular signal CD47-SIRPα system by binding to SIRPα, a membrane molecule expressed on macrophages (MΦ). This CD47-SIRPα system strongly suppresses antibody-dependent cellular phagocytosis (ADCP) by MΦs. In this study, we tried to develop a new antibody drug that can strongly induce ADCP activity against tumors under conditions that inhibit the CD47-SIRPα system. We obtained antibodies that have the potential to exhibit antitumor effects against various types of tumors.

Academic Significance and Societal Importance of the Research Achievements

本研究遂行の過程で得られた様々なデータには、MΦによる細胞貪食の制御機構について新たな知見をもたらす可能性があるものが含まれており、本研究の成果は学術的な観点から興味深いものであった。一方で、本研究では従来にない優れた抗腫瘍効果を示す抗体医薬の開発につながる成果を得ており、社会的意義のある成果となった。以上のことから、本研究の成果は基礎研究ならび革新的な治療薬開発に貢献することが期待できる成果であるといえる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (38 results)

All 2024 2023 2022 Other

All Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (29 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Bibliometric analysis of organoids in regenerative medicine-related research worldwide over two decades (2002?2022)2024

    • Author(s)
      Setiawan Jajar、Rizal Dicky Moch、Sofyantoro Fajar、Priyono Dwi Sendi、Septriani Nur Indah、Mafiroh Wulan Usfi、Kotani Takenori、Matozaki Takashi、Putri Wahyu Aristyaning
    • Journal Title

      Regenerative Medicine

      Volume: 19 Issue: 3 Pages: 119-133

    • DOI

      10.2217/rme-2023-0176

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD47 promotes peripheral T cell survival by preventing dendritic cell?mediated T cell necroptosis2023

    • Author(s)
      Komori Satomi、Saito Yasuyuki、Nishimura Taichi、Respatika Datu、Endoh Hiromi、Yoshida Hiroki、Sugihara Risa、Iida-Norita Rie、Afroj Tania、Takai Tomoko、Oduori Okechi S.、Nitta Eriko、Kotani Takenori、Murata Yoji、Kaneko Yoriaki、Nitta Ryo、Ohnishi Hiroshi、Matozaki Takashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 33 Pages: 1-1

    • DOI

      10.1073/pnas.2304943120

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeting of SIRPα as a potential therapy for Langerhans cell histiocytosis2023

    • Author(s)
      Okamoto Takeshi、Murata Yoji、Hasegawa Daiichiro、Yoshida Makiko、Tanaka Daisuke、Ueda Takashi、Hazama Daisuke、Oduori Okechi S.、Komori Satomi、Takai Tomoko、Saito Yasuyuki、Kotani Takenori、Kosaka Yoshiyuki、Maniwa Yoshimasa、Matozaki Takashi
    • Journal Title

      Cancer Science

      Volume: - Issue: 5 Pages: 1871-1881

    • DOI

      10.1111/cas.15758

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preclinical evaluation of the efficacy of an antibody to human SIRPα for cancer immunotherapy in humanized mouse models2023

    • Author(s)
      Saito Yasuyuki、Iida-Norita Rie、Afroj Tania、Refaat Alaa、Hazama Daisuke、Komori Satomi、Ohata Shinya、Takai Tomoko、Oduori Okechi S.、Kotani Takenori、Funakoshi Yohei、Koma Yu-Ichiro、Murata Yoji、Yakushijin Kimikazu、Matsuoka Hiroshi、Minami Hironobu、Yokozaki Hiroshi、Manz Markus G.、Matozaki Takashi
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1294814-1294814

    • DOI

      10.3389/fimmu.2023.1294814

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LAT1 expression influences Paneth cell number and tumor development in ApcMin/+ mice2023

    • Author(s)
      Yunlong Sui, Namiko Hoshi, Ryuichi Ohgaki, Ryutaro Yoshida, Yuzo Kodama, et al.
    • Journal Title

      Journal of Gastroenterology

      Volume: 58 Issue: 5 Pages: 444-457

    • DOI

      10.1007/s00535-023-01960-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer2023

    • Author(s)
      Omatsu Mayuki、Nakanishi Yuki、Kasashima Hiroaki、et al.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 5534-5534

    • DOI

      10.1038/s41467-023-41095-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lysosomal cholesterol overload in macrophages promotes liver fibrosis in a mouse model of NASH2023

    • Author(s)
      Itoh Michiko、Tamura Atsushi、Kanai Sayaka、Tanaka Miyako、Kanamori Yohei、Shirakawa Ibuki、Ito Ayaka、Oka Yasuyoshi、Hidaka Isao、Takami Taro、Honda Yasushi、Maeda Mitsuyo、Saito Yasuyuki、Murata Yoji、Matozaki Takashi、Nakajima Atsushi、Kataoka Yosky、Ogi Tomoo、Ogawa Yoshihiro、Suganami Takayoshi
    • Journal Title

      Journal of Experimental Medicine

      Volume: 220 Issue: 11

    • DOI

      10.1084/jem.20220681

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Role of Type-2 Conventional Dendritic Cells in the Regulation of Tumor Immunity2022

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

      Cancers

      Volume: 14 Issue: 8 Pages: 1976-1976

    • DOI

      10.3390/cancers14081976

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Protein tyrosine phosphatases and CD47-SIRPα signaling: physiological functions and therapeutic applications2024

    • Author(s)
      Takashi Matozaki
    • Organizer
      The 5th Japan-Taiwan Bilateral Conference on Protein Phosphatase
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Preclical evaluation of the efficacy of an antibody to human SIRPα for cancer immunotherapy in humanized mouse models2024

    • Author(s)
      Yasuyuki Saito,Tania Afroj,Satomi Komori,Tomoko Takai, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      The 5th Japan-Taiwan Bilateral Conference on Protein Phosphatase
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SIRPα, a potential therapeutic target for the head and neck cancer2024

    • Author(s)
      Takashi Ueda, Yoji Murata, Daisuke Tanaka, Oduori S. Okechi, Saki Matsumoto, Yasuyuki Saito, Takenori Kotani, Ken-Ichi Nibu, Takashi Matozaki
    • Organizer
      The 5th Japan-Taiwan Bilateral Conference on Protein Phosphatase
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD47 promotes peripheral T cell survival by preventing dendritic cell mediated T cell necroptosis2024

    • Author(s)
      Satomi Komori, Yasuyuki Saito, Tania Afrof, Tomoko Takai, Okechi S. Oduori, Takenori, Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第52回日本免疫学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Preclinical Evaluation of the Efficacy of Human Sirpα Antibodies for B-Cell Lymphoma Immunotherapy in Humanized Mose Models2023

    • Author(s)
      Yasuyuki Saito, Afroj Tania, Satomi Komori, Tomoko Takai, Oduori Okechi, Takenori Kotani, Yohei Funakoshi, Yoji Murata, Kimikazu Yakushijin, Hiroshi Matsuoka, Hironobu Minami, Markus G Manz, Takashi Matozaki
    • Organizer
      2023 ASH ANNUAL MEETING
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis2023

    • Author(s)
      Satomi Komori, Yasuyuki Saito, Tania Afrof, Tomoko Takai, Okechi S. Oduori, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of the novel cancer therapy by regulation of tumor cell phagocytosis through the CD47-SIRPα system2023

    • Author(s)
      Takenori Kotani, Tomoko Takai, Satomi Komori, Yoji Murata, Yasuyuki Saito, Takashi Matozaki
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Antitumor immune responses by modulating the function of SIRPβ1 in innate immune cells2023

    • Author(s)
      Yoji Murata, Oduori S. Okechi, Takashi Ueda, Mariko Sakamoto, Daisuke Taknaka, Takenori Kotani, Yasuyuki Saito, Takashi Matozaki
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis2023

    • Author(s)
      Yasuyuki Saito, Satomi Komori, Tania Afroj, Tomoko Takai, Oduori Okechi, Eriko Nitta, Takenori Kotani, Yoji Murata, Ryo Nitta, Takashi Matozaki
    • Organizer
      第85回日本血液学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Therapeutic potential of anti-SIRPβ1 antibodies and its mechanism of action in cancers2023

    • Author(s)
      Okechi S.Oduori, Daisuke Tanaka, Tomoko Takai, Takashi Ueda, Mariko Sakamoto, Takenori Kotani, Yasuyuki Saito, Takashi Matozaki, Yoji Murata
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 樹状細胞は膜分子CD47を介して抹消組織T細胞の生存を制御する2023

    • Author(s)
      小森里美, Tania Afroj, 高井智子, Oduori Okechi, 小谷武徳, 村田陽二, 的崎尚, 齊藤泰之
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 14.CD47欠損細胞の生体からの排除におけるCD11c+ SIRPα+樹状細胞の重要性2023

    • Author(s)
      高井智子, 小谷武徳, 小森里美, 齊藤泰之, 村田陽二, 的崎尚
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 細胞間シグナルCD47-SIRPα系による細胞の生存・維持と排除の分子機構2023

    • Author(s)
      的崎尚, 村田陽二, 齊藤泰之, 小谷武徳
    • Organizer
      群馬大学研究所記念内分泌代謝シンポジウム
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 頭頸部がんにおける治療標的候補分子SIRPα2023

    • Author(s)
      上田隆, 村田陽二, 田中大介, Oduori S.Okechi, 齊藤泰之, 小谷武徳, 丹生健一, 的崎尚
    • Organizer
      第21回生体機能研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of a novel cancer immunotherapy model targeting human macrophages2023

    • Author(s)
      Tania Afroj, Yasuyuki Saito, Satomi Komori, Tomoko Takai, Okechi S. Oduori, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第21回生体機能研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] CD47-SIRPα-Shp1 tyrosine phosphatase signaling: Importance for blood cell survival and function2023

    • Author(s)
      Takashi Matozaki
    • Organizer
      EMBO Workshop Signal regulation by protein phosphatases: Mechanisms and pathways
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミクログリア特異的SIRPα欠損が脳老化に与える影響 Effect of microglia-specific SIRPα knockout on brain aging2022

    • Author(s)
      水谷瑠衣、今井武史、富山飛鳥、松下紗世子、森田紋子、浦野江里子、林由里子、的崎尚、大西浩史
    • Organizer
      NEURO2022 第45回日本神経科学大会 第65回日本神経化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ミクログリアにおけるCX3CR1とSIRPαの機能的相互作用 Functional onteraction of CX3CR1 and SIRPαin microglia2022

    • Author(s)
      今井武史、水谷瑠衣、富山飛鳥、松下紗世子、森田紋子、浦野江里子、林由里子、的崎尚、大西浩史
    • Organizer
      NEURO2022 第45回日本神経科学大会 第65回日本神経化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 自然免疫系細胞の制御によるSIRPファミリー分子を標的とする新規がん治療法の開発 Targeting of SIRP family proteins provide as a new cancer therapy by control of innate immune cells2022

    • Author(s)
      的崎尚、村田陽二、齊藤泰之、小谷武徳
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] マクロファージ SIRPβ1を標的とした新たながん免疫療法 Targeting of SIRPβ1 on macrophages as a novel strategy for cancer immunotherapy2022

    • Author(s)
      村田陽二、坂本茉莉子、高井智子、齊藤泰之、小谷武徳、的崎尚
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新規ヒト化マウスを用いたマクロファージを介した抗腫瘍効果の前臨床評価モデル Preclinical evaluation of macrophage-mediated anti-tumor effct by using a novel humanized mouse model2022

    • Author(s)
      齊藤泰之、飯田理恵、小森里美、小谷武徳、村田陽二、横崎宏、的崎尚
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] マクロファージによるがん細胞貪食を制御する分子基盤の解明 Molecular basis of tumor cell phagocytosis by macrophage2022

    • Author(s)
      小谷武徳、高井智子、齊藤泰之、村田陽二、的崎尚
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 細胞間シグナルCD47-SIRPα系による細胞貪食制御機序とその新規がん治療法への応用 Regulation of cellular phagocytosis by the CD47-SIRPα system and its application to new cancer therapy2022

    • Author(s)
      小谷 武徳、高井智子、小森里美、齊藤 泰之、村田 陽二、的崎 尚
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 脳白質におけるSIRPα欠損ミクログリア活性化の領域特異性解析 Analysis of region specificity of SIRPα-deficient microglial activation in brain white matter2022

    • Author(s)
      尾池恵摘,水谷瑠依,今井武史,今田治子,榛澤春哉,正林大地,神宮大輝,林由里子,的崎尚、大西浩史
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Tyrosine phosphatases and CD47-SIRPα signaling: functions and therapeutic importance2022

    • Author(s)
      Takashi Matozaki
    • Organizer
      FASEB&JAPPR
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Dendritic cells regulate peripheral T cell survival through the CD47-SIRPαsignaling2022

    • Author(s)
      Yasuyuki Saito, Satomi Komori, Hiroki Yoshida, risa Sugihara, Tomoko Takai, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] SIRPαand CD47 promote cDC2 survival through the regulation of transcriptional factor Nr4a32022

    • Author(s)
      Satomi Komori, Yasuyuki Saito, Taichi Nishimura, Hiroki Yoshida, Risa Sugihara, Tomoko Takai, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Dendritic cells regulate peripheral T cell survival through the CD47-SIRPαsignaling2022

    • Author(s)
      Yasuyuki Saito, Satomi Komori, Hiroki Yoshida, Risa Sugihara, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      DC2022 国際樹状細胞学会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] SIRPαmaintains cDC2 survival by regulating the Nr4a3 expressin2022

    • Author(s)
      Satomi Komori, Yasuyuki Saito, Taichi Nishimura, Takenori Kotani, Yoji Murata, Takashi Matozaki
    • Organizer
      DC2022 国際樹状細胞学会
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Remarks] 神戸大学大学院医学研究科 生化学・分子生物学講座 生体シグナル制御学部門

    • URL

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

    • Related Report
      2023 Annual Research Report 2022 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2025-01-30  

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