Engineering of T cells with customized cancer therapeutic programs using synthetic notch receptor.
Project/Area Number |
18K09000
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Yokohama 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.
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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。
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Report
(4 results)
Research Products
(13 results)
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[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.
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Journal Title
Biochem Biophys Res Commun.
Volume: 534
Pages: 666-671
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J Mol Cell Biol.
Volume: 12
Issue: 12
Pages: 987-990
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Clin Cancer Res.
Volume: 印刷中
Issue: 14
Pages: 4375-4387
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Breast Cancer Res Treat.
Volume: 170(3)
Issue: 3
Pages: 507-516
DOI
Related Report
Peer Reviewed
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