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Cancer immnotherapy to augment antibody dependent cellular cytotoxicity

Research Project

Project/Area Number 17K10095
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionHirosaki University

Principal Investigator

Kudo Ko  弘前大学, 医学部附属病院, 助教 (20455728)

Co-Investigator(Kenkyū-buntansha) 土岐 力  弘前大学, 医学研究科, 講師 (50195731)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords細胞療法 / 免疫療法 / 遺伝子改変 / 抗体依存性細胞傷害 / 小児がん / 遺伝子治療 / キメラ型受容体 / キメラ受容体 / 免疫細胞療法 / 癌 / 免疫学 / 移植・再生医療 / トランスレーショナルリサーチ
Outline of Final Research Achievements

This study aims to establish the novel cell line-based cancer immunotherapy, which augments the antitumor effect in combination with therapeutic antibodis. We transduced Fc-receptor based chimeric antigen receptors into natural killer cell originated cell line NK-92 instead of primary T lymphocytes. We performed cytotoxicity assay to test the antitumor effect on tumor cell lines in the presence of the responsible therapeutic antibodies. We compared the capacity of the cell lines to those of the genetically modified primary lymphocytes and the existing products, which have been reported. The genetically modified NK-92 cell exerted antitumor effect. However, the efficacy was not superior to the existing products and even less than those of the genetically modified primary T-cells. We, therefore, continued to evaluate the durability of the cells and try to improve the chimeric receptor to increase the antitumor effect.

Academic Significance and Societal Importance of the Research Achievements

遺伝子改変免疫細胞療法は進歩が著しいが、患者由来のリンパ球を用いることにより、作成コスト、所要時間、および品質のばらつきが問題点である。本研究では細胞株の使用により、このような課題を解決できる可能性を有する新規治療法の開発に取り組んだ。残念ながら、現時点では抗腫瘍効果において難点があるため、また、先行研究に比べ優越性を示すことができなかった。今後、さらなる改良を進めていく必要がある。

Report

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

    (7 results)

All 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Comprehensive genetic analyses of relapsed B-cell precursor acute lymphoblastic leukemia in children2019

    • Author(s)
      Kaori Kubo, Ko Kudo, Tsutomu Toki, Rika Kanezaki, Fumika Ikeda, Tatsuya Ito, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Shinya Sasaki, Kiminori Terui, Etsuro Ito
    • Journal Title

      Hirosaki Medical Journal

      Volume: 70 Pages: 13-13

    • NAID

      130007757470

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zoledronic acid for relapsed Langerhans cell histiocytosis with isolated skull bone lesion.2019

    • Author(s)
      Kudo K, Tanaka T, Kobayashi A, Terui K, Ito E.
    • Journal Title

      Pediatr Int.

      Volume: 61 Issue: 3 Pages: 315-317

    • DOI

      10.1111/ped.13774

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Rapid Cytologic Double Staining of Epstein-Barr Virus-encoded Small RNA and Cell Surface Markers for Diagnosis of Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis2019

    • Author(s)
      Takahashi N, Kudo K, Tanaka M, Kumagai N, Sato T, Kamio T, Sasaki S, Terui K, Kurose A, Yanagisawa R, Nakazawa Y, Ito E.
    • Journal Title

      J Pediatr Hematol Oncol.

      Volume: - Issue: 8 Pages: 1-1

    • DOI

      10.1097/mph.0000000000001647

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] HNRNPH1-MLLT10融合遺伝子を検出した5q- AMLの1例2019

    • Author(s)
      工藤耕
    • Organizer
      第81回日本血液学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2.BRAF V600E-positive precursors as molecular markers of bone marrow involvement in pediatric langerhans cell histiocytosis2019

    • Author(s)
      Kudo K
    • Organizer
      The 61th American Society of Hematology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 3.BRAFV600E-POSITIVE PRECURSORS AS MOLECULAR MARKERS OF BONE MARROW INVOLVEMENT IN PEDIATRIC LANGERHANS CELL HISTIOCYTOSIS.2019

    • Author(s)
      Kudo K
    • Organizer
      The 35th Annual Meeting of the Histiocyte Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小児ランゲルハンス細胞組織球症における骨髄血中BRAF変異陽性細胞の意義についての検討2019

    • Author(s)
      工藤耕
    • Organizer
      第61回日本小児血液がん学会
    • Related Report
      2019 Annual Research Report

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

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