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Development of CD269-CAR T cells for the adoptive immunotherapy of multiple myeloma.

Research Project

Project/Area Number 16K18459
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionJichi Medical University

Principal Investigator

Uchibori Ryosuke  自治医科大学, 医学部, 講師 (20458285)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsキメラ抗原受容体 / CAR / CD269 / BCMA / 多発性骨髄腫 / 養子免疫遺伝子細胞治療 / 細胞療法 / 遺伝子治療 / 養子免疫療法 / がん免疫療法 / 造血器腫瘍
Outline of Final Research Achievements

Multiple myeloma (MM) remains in most cases an incurable disease, and new therapeutic strategies are urgently required for radical cure or continued disease control. Our purpose of this study is to verify whether treatment with CD269-specific CAR-expressing T cells can eradicate myeloma cells from bone marrow of tumor-bearing NOG mice. Firstly, we uniquely developed monoclonal antibodies against human CD269. Next, we designed and verified novel CD269-specific CAR. CD269-CAR T cells showed redirected cytolysis toward CD269-positive U266 human MM-derived cells, but not CD269-negative K562 cells. Six weeks after tumor inoculation, we injected saline, non-CAR gene-modified T cells, or CAR gene-modified T cells (GMCs) into the cardiac chamber of tumor-bearing mice. In the group of GMC injection, U266 cells were dramatically eradicated from bone marrow. We conclude that adoptive transfer of CD269-CAR T cells could be a promising option for patients with MM.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016

All Journal Article (3 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] CAR-T cell(キメラ抗原受容体発現T細胞)Therapy2018

    • Author(s)
      内堀亮介, 小澤敬也
    • Journal Title

      医薬ジャーナル

      Volume: 54 Pages: 79-85

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 多発性骨髄腫に対するCAR-T細胞療法の開発研究2017

    • Author(s)
      内堀亮介
    • Journal Title

      血液フロンティア

      Volume: 27 Pages: 49-56

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 多発性骨髄腫に対するキメラ抗原受容体T 細胞療法の可能性2017

    • Author(s)
      内堀亮介
    • Journal Title

      血液内科

      Volume: 74 Pages: 392-397

    • NAID

      40021144514

    • Related Report
      2017 Annual Research Report
  • [Presentation] CAR-T therapy for multiple myeloma.2017

    • Author(s)
      Uchibori R.
    • Organizer
      The 23rd Annual Meeting of the Japan Society of Gene Therapy.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] CD269(BCMA)を標的とした多発性骨髄腫に対するCAR-T療法2017

    • Author(s)
      内堀 亮介
    • Organizer
      第23回血液科学セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] CD269-CAR-T therapy for bone lesions in myeloma model mice.2017

    • Author(s)
      Uchibori R, Ohmine K, Mineno J, Takesako K, and Ozawa K.
    • Organizer
      The 8th JSH International Symposium.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of CAR-T therapy on bone lesions in an orthotopic multiple myeloma mouse model.2017

    • Author(s)
      Uchibori R, Ohmine K, Sehara Y, Urabe M, Mizukami H, Mineno J, Takesako K, and Ozawa K.
    • Organizer
      20th Annual Meeting of the American Society of Gene & Cell Therapy.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] AR-T療法の基礎2017

    • Author(s)
      内堀 亮介
    • Organizer
      第32回悪性リンパ腫治療研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Therapeutic efficacy of CD269-specific CAR T cells in an orthotopic mouse model of multiple myeloma.2016

    • Author(s)
      Ryosuke Uchibori, Takeshi Teruya, Ken Ohmine, Masashi Urabe, Yasushi Saga, Hiroaki Mizukami, Junichi Mineno, and Keiya Ozawa.
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Therapeutic efficacy of CD269-targeted CAR-modified T cells in an orthotopic mouse model of multiple myeloma.2016

    • Author(s)
      Ryosuke Uchibori, Ken Ohmine, Masashi Urabe, Hiroaki Mizukami, Junichi Mineno, and Keiya Ozawa.
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-10-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Efficacy of adoptive immunotherapy with 269-CAR T cells in an orthotopic NOG mouse-human tumor xenograft model.2016

    • Author(s)
      内堀 亮介、照屋 武志、大嶺 謙、峰野 純一、小澤 敬也
    • Organizer
      第8回血液疾患免疫療法学会
    • Place of Presentation
      北海道大学医学部学友会館(北海道、札幌市)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] CD269-targeted CAR-modified T cells showed promising therapeutic efficacy in an orthotopic mouse model of multiple myeloma.2016

    • Author(s)
      Ryosuke Uchibori, Takeshi Teruya, Ken Ohmine, Masashi Urabe, Yasushi Saga, Hiroaki Mizukami, Junichi Mineno, and Keiya Ozawa.
    • Organizer
      第22回日本遺伝子細胞治療学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都、港区)
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Assessment of the efficacy and safety of CD269-specific CAR-expressing T cells using an orthotopic multiple myeloma mouse model.2016

    • Author(s)
      Ryosuke Uchibori, Takeshi Teruya, Ken Ohmine, Junichi Mineno, Kazuto Takesako, and Keiya Ozawa.
    • Organizer
      The 7th JSH International Symposium
    • Place of Presentation
      淡路夢舞台(兵庫県、淡路市)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] CD269 (BCMA)-specific CAR-expressing T cells dramatically eradicate myeloma cells from bone marrow of an orthotopic multiple myeloma mouse model.2016

    • Author(s)
      Ryosuke Uchibori, Takeshi Teruya, Ken Ohmine, Masashi Urabe, Yasushi Saga, Hiroaki Mizukami, Junichi Mineno, Kazuto Takesako, and Keiya Ozawa.
    • Organizer
      The 19th Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Washington, D.C., USA.
    • Year and Date
      2016-05-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2019-03-29  

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