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Engineering of T cells with customized cancer therapeutic programs using synthetic notch receptor.

Research Project

Project/Area Number 18K09000
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionYokohama City University

Principal Investigator

NISHI Mayuko  横浜市立大学, 医学研究科, 助教 (90635343)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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)
Keywords脳腫瘍 / 悪性リンパ腫 / ウイルス / 腫瘍免疫
Outline of Final Research Achievements

Primary central nervous system lymphoma (PCNSL) is a rare type of highly malignant non-Hodgkin lymphoma, which arises in the central nervous system. In our current study, we aimed to develop a new immunotherapy platform by combining therapies with oncolytic virus and chimeric antigen receptor(CAR)T cell. We initially established nine patient-derived PCNSL cell lines (PDCs) and found that PCNSLs are highly susceptible to infection with NDV. Next, we constructed single-chain variable fragment (scFV) against NDV-HN antigen. The anti-NDV-HN scFv was fused with synNotch gene and introduced into Jurkat T cells for creating NDV sensing cells. Co-culture of the synNotch-Jurkat cells with NDV-infected PCNSL-PDCs resulted in the induction of CD19-specific CAR. On the other hand, there was no significant cell cytotoxicity of PCNSL-PDCs by the co-culture probably due to low expression of CAR on the cell surface.

Academic Significance and Societal Importance of the Research Achievements

現在実施されているPCNSLに対する免疫細胞療法は、臨床試験において比較的高い有効性を示したが、その投与方法や副作用など未だ解決できていない課題が山積している。一方、腫瘍溶解ウイルスを用いた抗腫瘍療法は、ウイルスによる直接的な細胞障害作用とともに、宿主による腫瘍免疫を増強する効果があることが知られている。本研究課題では、近年開発された、改変Notch技術を活用し、上記の2つの抗腫瘍戦略を融合し、発展させる効果が期待される。本アプローチが成功すれば、PCNSLに対する特異性および有効性の高い細胞免疫療法の発展が期待できる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018 Other

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (1 results) Remarks (1 results)

  • [Journal Article] Zika virus protease induces caspase-independent pyroptotic cell death by directly cleaving gasdermin D2021

    • Author(s)
      Yamaoka Y, Matsunaga S, Jeremiah SS, Nishi M, Miyakawa K, Morita T, Khatun H, Shimizu H, Okabe N, Kimura H, Hasegawa H, Ryo A.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 534 Pages: 666-671

    • DOI

      10.1016/j.bbrc.2020.11.023

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbonic anhydrase 13 suppresses bone metastasis in breast cancer2021

    • Author(s)
      Yogosawa Satomi、Nakayama Jun、Nishi Mayuko、Ryo Akihide、Yoshida Kiyotsugu
    • Journal Title

      Cancer Treatment and Research Communications

      Volume: 27 Pages: 100332-100332

    • DOI

      10.1016/j.ctarc.2021.100332

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid quantitative screening assay for SARS-CoV-2 neutralizing antibodies using HiBiT-tagged virus-like particles2021

    • Author(s)
      Miyakawa K, Jeremiah SS, Ohtake N, Matsunaga S, Yamaoka Y, Nishi M, Morita T, Saji R, Nishii M, Kimura H, Hasegawa H, Takeuchi I, Ryo A.
    • Journal Title

      J Mol Cell Biol.

      Volume: 12 Issue: 12 Pages: 987-990

    • DOI

      10.1093/jmcb/mjaa047

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Monoclonal Antibodies and Antigen-Capture ELISA for Human Parechovirus Type 3.2020

    • Author(s)
      Goto K, Yamaoka Y, Khatun H, Miyakawa K, Nishi M, Nagata N, Yanaoka T, Kimura H, Ryo A.
    • Journal Title

      Microorganisms.

      Volume: 8 Issue: 9 Pages: 1437-1437

    • DOI

      10.3390/microorganisms8091437

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Hyperactive RelA/p65-Hexokinase 2 Signaling Axis Drives Primary Central Nervous System Lymphoma2020

    • Author(s)
      Tateishi Kensuke、Miyake Yohei、Kawazu Masahito、Sasaki Nobuyoshi、Nakamura Taishi、Sasame Jo、Yoshii Yukie、Ueno Toshihide、Miyake Akio、Matsushita Yuko、Shiba Norio、Udaka Naoko、Ohki Kentaro、Fink Alexandria L.、Tummala Shilpa S.、Natsumeda Manabu、Miller Julie J.、Fujii Yukihiko、et al
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 23 Pages: 5330-5343

    • DOI

      10.1158/0008-5472.can-20-2425

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolyl Isomerase Pin1 Regulates the Stability of Hepatitis B Virus Core Protein.2020

    • Author(s)
      Nishi M, Miyakawa K, Matsunaga S, Khatun H, Yamaoka Y, Watashi K, Sugiyama M, Kimura H, Wakita T, Ryo A.
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 26-26

    • DOI

      10.3389/fcell.2020.00026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation2019

    • Author(s)
      Miyakawa Kei、Matsunaga Satoko、Yokoyama Masaru、Nomaguchi Masako、Kimura Yayoi、Nishi Mayuko、Kimura Hirokazu、Sato Hironori、Hirano Hisashi、Tamura Tomohiko、Akari Hirofumi、Miura Tomoyuki、Adachi Akio、Sawasaki Tatsuya、Yamamoto Naoki、Ryo Akihide
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1844-1844

    • DOI

      10.1038/s41467-019-09867-7

    • NAID

      120006949469

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PI3K/AKT/mTOR pathway alterations promote malignant progression and xenograft formation in oligodendroglial tumors.2019

    • Author(s)
      Tateishi K, Nakamura T, Juratli TA, Williams EA, Matsushita Y, Miyake S, Nishi M, Miller JJ, Ryo A, Yamanaka S, Curry WT, Dias-Santagata D, Yamamoto T, Ichimura K, Batchelor T, Chi AS, Iafrate AJ, Wakimoto H, Cahill DP, et al.
    • Journal Title

      Clin Cancer Res.

      Volume: 印刷中 Issue: 14 Pages: 4375-4387

    • DOI

      10.1158/1078-0432.ccr-18-4144

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel inhibitor of tumorspheres reveals the activation of the serine biosynthetic pathway upon mitochondrial inhibition.2019

    • Author(s)
      Subedi A, Muroi M, Futamura Y, Kawamura T, Aono H, Nishi M, Ryo A, Watanabe N, Osada H.
    • Journal Title

      FEBS Lett.

      Volume: 593 Issue: 8 Pages: 763-776

    • DOI

      10.1002/1873-3468.13361

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TROY expression is associated with pathological stage and poor prognosis in patients treated with radical cystectomy.2019

    • Author(s)
      Nomura M, Matsumoto K, Shimizu Y, Ikeda M, Amano N, Nishi M, Ryo A, Nagashio R, Sato Y, Iwamura M.
    • Journal Title

      Cancer Biomark.

      Volume: 24(1) Issue: 1 Pages: 91-96

    • DOI

      10.3233/cbm-181911

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness.2018

    • Author(s)
      Shima H, Kida K, Adachi S, Yamada A, Sugae S, Narui K, Miyagi Y, Nishi M, Ryo A, Murata S, Taniguchi H, Ichikawa Y, Ishikawa T, Endo I.
    • Journal Title

      Breast Cancer Res Treat.

      Volume: 170(3) Issue: 3 Pages: 507-516

    • DOI

      10.1007/s10549-018-4793-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ビトリゲル膜を介した両面培養による中枢神経系原発悪性リンパ腫細胞と脳血管周皮細胞との相互作用解析2019

    • Author(s)
      西 真由子,立石健祐, 畑山靖佳, 山岡悠太郎, 山本哲哉, 梁 明秀
    • Organizer
      第42回分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 横浜市立大学大学院医学研究科 微生物学・分子生体防御学

    • URL

      https://www-user.yokohama-cu.ac.jp/~saikin/?page_id=54

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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