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Development of patient-derived cancer on-a-chip devices for cancer immunotherapy

Research Project

Project/Area Number 17H02082
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKyoto University

Principal Investigator

Torisawa Yu-suke  京都大学, 白眉センター, 特定准教授 (10767354)

Co-Investigator(Kenkyū-buntansha) 井上 匡美  京都府立医科大学, 医学(系)研究科(研究院), 教授 (10379232)
金子 新  京都大学, iPS細胞研究所, 准教授 (40361331)
高山 浩一  京都府立医科大学, 医学(系)研究科(研究院), 教授 (50274444)
三嶋 雄太  京都大学, iPS細胞研究所, 特定研究員 (80770263)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsがん評価モデル / マイクロ流体デバイス / がん免疫 / がんオルガノイド / 3次元培養 / 再生医学 / iPS細胞 / 3次元培養法 / Organ-on-a-chip / がん免疫細胞療法 / がんの評価モデル / organ-on-a-chip / がんモデル / 組織培養 / 血管 / マイクロ・ナノデバイス / 癌 / 免疫学
Outline of Final Research Achievements

The aim of this study is to develop microdevices to maintain 3D tumor-like tissue constructs. By mimicking the tumor microenvironment, we developed a vascularized cancer-on-a-chip microdevice that allows a vascular network to be connected to a 3D cancer spheroid so immune cells can be perfused through blood vessels. By combining with iPS cell technology, we engineered vascular networks using HLA-knockout human iPSC-derived endothelial cells within microfluidic devices. We demonstrated that T cells could be cultured within the engineered blood vessels. This cancer-on-a-chip microdevice can be used to evaluate immune responses through a vascular network to test anticancer effects of T cells. Furthermore, this device can be used to culture tumor biopsies harvested from patients. Therefore, we have successfully developed a novel platform to culture a 3D tumor-like tissue construct generated from a patient's tumor biopsy, which allows to test the effect of T cells for cancer immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

免疫細胞療法は、第4のがん治療法として期待が高まる一方で、固形癌に対する効果は未だに限定的であり、メカニズムの解明が急務となっている。本研究で開発した評価手法は、からだの外で、T細胞とがん組織との相互作用が追跡評価でき、T細胞の抗腫瘍機能が評価可能であるため、作製したT細胞が、いかにして腫瘍に作用し効果を発揮するのか、また実際に抗腫瘍効果を示すのかどうか、評価が可能となる。また、患者由来の腫瘍組織を用いても評価が可能であるため、個々の患者に対する免疫細胞療法の効果が予測できる可能性を有しており、基礎学術的に新たな知見が得られるだけでなく、有効性の評価や治療技術の向上などの社会的な意義も大きい。

Report

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

    (53 results)

All 2020 2019 2018 2017

All Journal Article (24 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (27 results) (of which Int'l Joint Research: 11 results,  Invited: 17 results) Book (2 results)

  • [Journal Article] Non-clinical efficacy, safety, and stable clinical cell processing of iPSC-derived anti-GPC3 CAR-expressing NK/ILC cells.2020

    • Author(s)
      Ueda T., Kumagai A., Iriguchi S., Yasui Y., Miyasaka T., Nakagoshi K., Nakane K., Saito K., Takahashi M., Sasaki A., Yoshida S., Takasu N., Seno H., Uemura Y., Tamada K., Nakatsura T., Kaneko S.
    • Journal Title

      Cancer Sci.

      Volume: in press Issue: 5 Pages: 1-13

    • DOI

      10.1111/cas.14374

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomimetic aorta-gonad-Mesonephros-on-a-Chip to study human developmental hematopoiesis.2020

    • Author(s)
      Sugimura R1, Ohta R1, Mori C2, Li A1, Mano T1, Sano E2, Kosugi K2, Nakahata T1, Niwa A1, Saito MK3, Torisawa YS4,5.
    • Journal Title

      Biomed Microdevices.

      Volume: 2 Issue: 2 Pages: 22-34

    • DOI

      10.1007/s10544-020-00488-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] マイクロメカノデバイス2020

    • Author(s)
      鳥澤勇介
    • Journal Title

      実験医学

      Volume: 38 Pages: 196-201

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Tetrafluoroethylene-Propylene Elastomer for Fabrication of Microfluidic Organs-on-Chips Resistant to Drug Absorption2019

    • Author(s)
      Sano Emi、Mori Chihiro、Matsuoka Naoki、Ozaki Yuka、Yagi Keisuke、Wada Aya、Tashima Koichi、Yamasaki Shinsuke、Tanabe Kana、Yano Kayo、Torisawa Yu-suke
    • Journal Title

      Micromachines

      Volume: 10 Issue: 11 Pages: 793-793

    • DOI

      10.3390/mi10110793

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of age-dependent changes in cell size on endothelial cell proliferation and senescence through YAP12019

    • Author(s)
      Mammoto Tadanori、Torisawa Yu-suke、Muyleart Megan、Hendee Kathryn、Anugwom Charles、Gutterman David、Mammoto Akiko
    • Journal Title

      Aging

      Volume: 11 Issue: 17 Pages: 7051-7069

    • DOI

      10.18632/aging.102236

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Volume-Based Consolidation-to-Tumor Ratio Is a Useful Predictor for Postoperative Upstaging in Stage I and II Lung Adenocarcinomas2019

    • Author(s)
      Shimomura Masanori、Iwasaki Masashi、Ishihara Shunta、Inoue Masayoshi
    • Journal Title

      The Thoracic and Cardiovascular Surgeon

      Volume: 2019 Issue: 03 Pages: 1-1

    • DOI

      10.1055/s-0039-1694061

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparing three different anti-PD-L1 antibodies for immunohistochemical evaluation of small cell lung cancer2019

    • Author(s)
      Yoshimura Akihiro、Yamada Tadaaki、Miyagawa-Hayashino Aya、Sonobe Yuta、Imabayashi Tatsuya、Yamada Takahiro、Okada Satoru、Shimamoto Takayuki、Chihara Yusuke、Iwasaku Masahiro、Kaneko Yoshiko、Uchino Junji、Inoue Masayoshi、Konishi Eiichi、Takayama Koichi
    • Journal Title

      Lung Cancer

      Volume: 137 Pages: 108-112

    • DOI

      10.1016/j.lungcan.2019.09.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Feasibility of postoperative adjuvant chemotherapy using carboplatin plus S-1 in completely resected non-small cell lung cancer patients2019

    • Author(s)
      Inoue Masayoshi、Kusumoto Hidenori、Shiono Hiroyuki、Shintani Yasushi、Ose Naoko、Sakamaki Yasushi、Okami Jiro、Higashiyama Masahiko、Takeuchi Yukiyasu
    • Journal Title

      Journal of Chemotherapy

      Volume: 31 Issue: 6 Pages: 343-348

    • DOI

      10.1080/1120009x.2019.1651002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マイクロ流体デバイスを用いた血管ネットワークの形成とOrgan-on-a-chipへの応用2019

    • Author(s)
      鳥澤勇介
    • Journal Title

      Drug Delivery System

      Volume: 34 Pages: 268-277

    • NAID

      130007772603

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 微小流体デバイスを用いたiPS細胞研究の進展2019

    • Author(s)
      鳥澤勇介、横川隆司
    • Journal Title

      BIO Clinica

      Volume: 34 Pages: 30-35

    • Related Report
      2019 Annual Research Report
  • [Journal Article] In Vitro Differentiation of T Cells: From Nonhuman Primate-Induced Pluripotent Stem Cells2019

    • Author(s)
      Iriguchi Shoichi、Kaneko Shin
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 93-106

    • DOI

      10.1007/978-1-4939-9728-2_11

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Redifferentiation of Adaptive Na?ve-Like CTL from T-Cell-Derived iPSC2019

    • Author(s)
      Kawai Yohei、Kaneko Shin
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 71-75

    • DOI

      10.1007/978-1-4939-9728-2_7

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vitro Differentiation of T Cell: From Human iPS Cells in Feeder-Free Condition2019

    • Author(s)
      Yasui Yutaka、Hitoshi Yasumichi、Kaneko Shin
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 77-80

    • DOI

      10.1007/978-1-4939-9728-2_8

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Differentiating CD8αβ T Cells from TCR-Transduced iPSCs for Cancer Immunotherapy2019

    • Author(s)
      Minagawa Atsutaka、Kaneko Shin
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 81-84

    • DOI

      10.1007/978-1-4939-9728-2_9

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
  • [Journal Article] In Vitro Differentiation of T Cell: From CAR-Modified T-iPSC2019

    • Author(s)
      Ueda Tatsuki、Kaneko Shin
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 85-91

    • DOI

      10.1007/978-1-4939-9728-2_10

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
  • [Journal Article] In Vitro Detection of Cellular Adjuvant Properties of Human Invariant Natural Killer T Cells2019

    • Author(s)
      Zhang Rong、Kitayama Shuichi、Liu Tianyi、Ueda Norihiro、Tokumitsu Yumi、Mashima Hiroaki、Ohdan Hideki、Kaneko Shin、Uemura Yasushi
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 121-130

    • DOI

      10.1007/978-1-4939-9728-2_13

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vitro Differentiation of T Cells: From Human Embryonic Stem Cells and Induced Pluripotent Stem Cells2019

    • Author(s)
      Iriguchi Shoichi、Kaneko Shin
    • Journal Title

      Methods Mol Biol

      Volume: 2048 Pages: 59-70

    • DOI

      10.1007/978-1-4939-9728-2_6

    • ISBN
      9781493997275, 9781493997282
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Developing thymus-on-a-chip and cancer-on-a-chip for cancer immunotherapy2019

    • Author(s)
      Torisawa Y, Mishima Y, Kaneko S
    • Journal Title

      Impact

      Volume: 2019 Issue: 2 Pages: 33-35

    • DOI

      10.21820/23987073.2019.2.33

    • Related Report
      2018 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Engineering bone marrow-on-a-chip2019

    • Author(s)
      Torisawa Y
    • Journal Title

      Microphysiological Systems

      Volume: 3 Pages: 1-3

    • DOI

      10.21037/mps.2019.02.01

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] マイクロ流体デバイス技術を用いたOrgan-on-a-chipの開発2018

    • Author(s)
      鳥澤勇介
    • Journal Title

      Pharmstage

      Volume: 7 Pages: 6-11

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network2018

    • Author(s)
      Emi Sano, Chihiro Mori, Yuji Nashimoto, Ryuji Yokokawa, Hidetoshi Kotera, and Yu-suke Torisawa
    • Journal Title

      Biomicrofluidics

      Volume: 印刷中 Issue: 4

    • DOI

      10.1063/1.5027183

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Organ-on-a-chip技術と骨髄模倣デバイスの開発2018

    • Author(s)
      鳥澤勇介
    • Journal Title

      化学とマイクロ・ナノシステム

      Volume: 3 Pages: 7-12

    • NAID

      40021536695

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Organ-on-a-chip: 動物実験に代わる薬物の新たな評価手法の開発2017

    • Author(s)
      鳥澤勇介、梨本裕司、横川隆司
    • Journal Title

      ぶんせき

      Volume: 8 Pages: 349-356

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 生体臓器の機能再現に向けたOrgan-on-a-chip技術の開発2017

    • Author(s)
      鳥澤勇介
    • Journal Title

      バイオサイエンスとインダストリー

      Volume: 76 Pages: 390-395

    • NAID

      40021341154

    • Related Report
      2017 Annual Research Report
  • [Presentation] Engineering of a vascularized 3D cell construct on-chip using human iPSC-derived cells2019

    • Author(s)
      Torisawa Yu-suke
    • Organizer
      Microfluidic & Organ-on-a-Chip Asia 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Engineering of iPSC-based organs-on-chips to model intestinal function2019

    • Author(s)
      Torisawa Yu-suke
    • Organizer
      日本薬物動態学会第34回年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Development of 3D cell constructs with perfusable vascular networks generated from iPSC-derived endothelial cells2019

    • Author(s)
      Torisawa Yu-suke
    • Organizer
      17th International Conference on Biomedical Engineering
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of iPSC-based CAR-T cell immunotherapy, CiRA 2019 International Symposium -iPSCs Changing the Future of Science and Medicine2019

    • Author(s)
      Kaneko Shin
    • Organizer
      CiRA 2019 International Symposium -iPSCs Changing the Future of Science and Medicine-
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 免疫再生治療の実現に向けて2019

    • Author(s)
      金子新
    • Organizer
      NPO法人愛媛がんサポートおれんじの会講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] がん治療への応用を目指した再生T細胞研究2019

    • Author(s)
      金子新
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いたがん免疫療法の開発2019

    • Author(s)
      金子新
    • Organizer
      淡路医師会8月の勉強会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] シングルセルテクノロジーを用いたiPS細胞由来T細胞の解析2019

    • Author(s)
      金子新
    • Organizer
      Single-Cell 2019 OSAKAセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Regeneration of Antigen-specific Cytotoxic T cells with an iPSC Technology2019

    • Author(s)
      Kaneko Shin
    • Organizer
      IAAO国際フォーラム2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy2019

    • Author(s)
      南川淳隆
    • Organizer
      第15回血液学若手研究者勉強会(麒麟塾)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] iPS細胞とレギュラトリーサイエンス2019

    • Author(s)
      三嶋雄太
    • Organizer
      順天堂大学医療の経済学 第10回授業
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の特性を生かしたがん免疫再生治療2019

    • Author(s)
      金子新
    • Organizer
      LINK-Jシンポジウム「がん医療のイノベーション
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Postoperative complications and long- term survival among octogenarians treated surgically for non-small cell lung cancer2019

    • Author(s)
      Shimomura M、Tsunezuka H、Okada S、Ishihara S、Ishikawa N、Ikebe S、Furuya T、Kameyama K、Kitaoka S、Shimada J、Inoue M
    • Organizer
      20th World Congress on Lung Cancer
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prediction of visceral pleural invasion in c-N0 non-small cell lung cancer2019

    • Author(s)
      Okada S、Hattori A、Matsunaga T、Takamochi K、Oh S、Inoue M、Suzuki K
    • Organizer
      20th World Congress on Lung Cancer
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 頭頸部扁平上皮癌における原発巣と肺転移巣でのPD-L1発現と予後2019

    • Author(s)
      岡田悟、伊東恭子、石原駿太、島田順一、加藤大志朗、下村雅律、常塚啓彰、池部智之、井上匡美
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Spread Through Air Spacesを生じた肺癌における画像・病理学的浸潤形態の特徴2019

    • Author(s)
      池部智之,下村雅律,常塚啓彰,岡田悟,石原駿太,鈴木啓史,石川成美,西村友樹,島田順一,井上匡美
    • Organizer
      第36回日本呼吸器外科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Engineering of Perfusable 3D Vascularized Tumor-on-a-Chip Using hiPSC-derived Endothelial cells2019

    • Author(s)
      三嶋雄太、早稲田真澄、高久保瞳、王博、佐野絵美、森千尋、金子新、鳥澤勇介
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マイクロ流体デバイスによる生体機能の再現2019

    • Author(s)
      鳥澤勇介
    • Organizer
      第401回CBI学会研究講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Organ-on-chipを用いた動物試験代替法の開発2019

    • Author(s)
      鳥澤勇介
    • Organizer
      神戸再生医療勉強会「オルガノイド研究で繋ぐ未来の医療」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Organ-on-chipによる薬剤効果検証デバイス2019

    • Author(s)
      鳥澤勇介
    • Organizer
      日本学術振興会 第131委員会第293回研究会「生体適合/非適合 薄膜・表面・界面技術」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Microfluidic Tissue Engineering of a 3D Vascularized Tissue-on-a-Chip using Human iPSC-derived Cells to Study Cancer Immunotherapy2018

    • Author(s)
      Torisawa Y, Mishima Y, Sano E, Waseda M, Takakubo H, Mori C, Iriguchi S, Kaneko S
    • Organizer
      5th Tissue Engineering and Regenerative Medicine International Society World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Engineering of a 3D Vascularized Tissue-on-a-Chip using Human iPSC-derived Cells2018

    • Author(s)
      Torisawa Y, Mishima Y, Sano E, Takakubo H, Mori C, Kaneko S
    • Organizer
      22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of a 3D vascularized cancer-on-a-chip platform using hiPSC-derived endothelial cells2018

    • Author(s)
      Torisawa Y, Mishima Y, Sano E, Mori C, Takakubo H, Kaneko S
    • Organizer
      EMBS Micro and Nanotechnology in Medicine Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic Tissue Engineering of a 3D Vascularized Tissue-on-a-Chip using Human iPSC-derived Cells to Study Cancer Immunotherapy2018

    • Author(s)
      Yu-suke Torisawa, Yuta Mishima, Emi Sano, Masazumi Waseda, Hitomi Takakubo, Chihiro Mori, Shoichi Iriguchi, Shin Kaneko
    • Organizer
      5th Tissue Engineering and Regenerative Medicine International Society World Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MICROFLUIDIC TISSUE ENGINEERING OF PERFUSABLE 3D VASCULAR NETWORKS ON A CHIP USING HUMAN IPS CELLS2017

    • Author(s)
      Yuta Mishima, Masazumi Waseda, Emi Sano, Shoichi Iriguchi, Yutaka Yasui, Shin Kaneko, Yu-suke Torisawa
    • Organizer
      International Society for Stem Cell Research 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Organ-on-a-chip技術:骨髄模倣デバイスの開発2017

    • Author(s)
      鳥澤勇介
    • Organizer
      化学とマイクロ・ナノシステム学会第36回研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Organ-on-a-chip技術の開発と骨髄機能の再現への応用2017

    • Author(s)
      鳥澤勇介
    • Organizer
      第5回細胞凝集研究会2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] Applications of Microfluidic Systems in Biology and Medicine2019

    • Author(s)
      Torisawa Y
    • Total Pages
      20
    • Publisher
      Springer
    • Related Report
      2018 Annual Research Report
  • [Book] 歯科再生医学2019

    • Author(s)
      鳥澤勇介
    • Total Pages
      12
    • Publisher
      医歯薬出版
    • Related Report
      2018 Annual Research Report

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

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