• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of Novel Immunotherapy of Cancer: NKp44-based Chimeric Antigen Receptors and Methods for Ex Vivo NK cell Expansion

Research Project

Project/Area Number 16K10015
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Imai Chihaya  新潟大学, 医歯学系, 准教授 (90419284)

Co-Investigator(Renkei-kenkyūsha) IMAMURA MASARU  新潟大学, 医歯学総合病院, 講師 (80464006)
Takachi Takayuki  新潟大学, 医歯学総合病院, 特任助教 (70444164)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsキメラ抗原受容体 / NK細胞 / CAR-T細胞 / NK細胞受容体 / NKp44 / がん免疫療法 / CAR / cancer immunotherapy / sarcoma / solid tumor / Natural killer cell / 難治がん / 白血病 / 細胞療法 / 遺伝子改変リンパ球 / cytotoxic T cell / childhood cancer
Outline of Final Research Achievements

We have developed novel chimeric antigen receptors (CAR) as well as a novel method for ex vivo natural killer cell (NK) expansion. We tried to optimize methodology to propagate NK cells with a feeder cell line, K562-mb15-41BBL, by changing several parameters, such as culture medium, E/T ratio, timing of irradiation, and additional drugs. We constructed a variety of CARs that utilize immunoglobulin domain of NKp44 receptor as an antigen-binding portion, which were tested for their surface expression and resulting functional diversities. Following completion of construction of 1st generation CAR, we also optimized the structure of 2nd generation 4-1BB-based NKp44-CAR. Primary human T cells or NK cells, transduced with NKp44-based CAR, are able to express the CAR protein on the cell surface, produce cytokines, and exert strong cytotoxic effects against a wide variety of leukemia cells and solid tumor cells.

Academic Significance and Societal Importance of the Research Achievements

近年、難治性の急性リンパ性白血病およびリンパ腫に対するキメラ抗原受容体遺伝子導入T細胞(CAR-T)療法の目覚ましい成果が報告されている。CAR-T療法は急性骨髄性白血病や種々の固形腫瘍への応用が期待されているが、適切な標的抗原の選択が難しく、いまだに成功例はほとんどない。本研究では、体外増幅NK細胞療法から発展し、T細胞にNK細胞様の選択性を付与できるCAR遺伝子を作成した。B細胞性腫瘍以外の悪性腫瘍に対するCAR-T療法の開発においては、標的抗原ロスや免疫抑制的がん微小環境などの克服すべき問題点が多いが、NKp44-CARはその幅広い対象疾患から有力な候補となり得る。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (30 results)

All 2019 2018 2017 2016

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Invited: 6 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] CAR-T細胞療法-遺伝子改変T細胞を用いた新しいがん治療2018

    • Author(s)
      今井千速
    • Journal Title

      小児科

      Volume: 59 Pages: 1583-1591

    • Related Report
      2018 Annual Research Report
  • [Journal Article] がん免疫療法:最近話題のPD-1抗体からCAR-T療法まで2018

    • Author(s)
      今井千速
    • Journal Title

      新潟県小児科医会会報

      Volume: 60 Pages: 17-20

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation.2017

    • Author(s)
      Hosokai R, Masuko M, Shibasaki Y, Saitoh A, Furukawa T, Imai C.
    • Journal Title

      Biol Blood Marrow Transplant.

      Volume: 23(4) Issue: 4 Pages: 606-611

    • DOI

      10.1016/j.bbmt.2016.12.638

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful treatment of histiocytic sarcoma with cladribine and high-dose cytosine arabinoside in a child2017

    • Author(s)
      Iwabuchi H, Kawashima H, Umezu H, Takachi T, Imamura M, Saitoh A, Ogose A, Imai C.
    • Journal Title

      Int J Hematol.

      Volume: 106 Issue: 2 Pages: 299-303

    • DOI

      10.1007/s12185-017-2202-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphicIKBKG/NEMO mutations2017

    • Author(s)
      Miot C, Imai K, Imai C, Mancini AJ, Kucuk XY, Kawai T, Nishikomori R, Ito E, Pellier I, Girod SD, Rosain J, Sasaki S, Casanova JL, Orange JS, and Picard C et al.
    • Journal Title

      Blood.

      Volume: 130 Issue: 12 Pages: 1456-1467

    • DOI

      10.1182/blood-2017-03-771600

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] キメラ抗原受容体 (CAR): 人工受容体遺伝子を導入したリンパ球による新たながん治療.2017

    • Author(s)
      今井千速.
    • Journal Title

      新潟医学会雑誌.

      Volume: 131 Pages: 7-10

    • NAID

      120006761894

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 白血病に対する新しい薬物・細胞治療2017

    • Author(s)
      今井千速.
    • Journal Title

      日本医師会雑誌.

      Volume: 145 Pages: 2600-2604

    • Related Report
      2017 Research-status Report
  • [Journal Article] 新潟県に子ども病院は必要か? ~小児科医の視点から.2017

    • Author(s)
      今井千速.
    • Journal Title

      新潟医学会雑誌.

      Volume: 131 Pages: 565-568

    • Related Report
      2017 Research-status Report
  • [Journal Article] 軟部組織病変を呈し特異な臨床経過を示したランゲルハンス細胞組織球症の1例.2017

    • Author(s)
      古寺 一樹, 今村 勝, 高地 貴行, 申 将守, 笠原 靖史, 岩渕 晴子, 川島 寛之, 生越 章, 梅津 哉, 齋藤 昭彦, 今井 千速.
    • Journal Title

      日本小児血液・がん学会雑誌.

      Volume: 54 Pages: 157-160

    • NAID

      130005960310

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] キメラ抗原受容体 (CAR): 人工受容体遺伝子を導入したリンパ球による新たながん治療.2017

    • Author(s)
      今井千速
    • Journal Title

      新潟医学会雑誌

      Volume: 131 Pages: 7-10

    • NAID

      120006761894

    • Related Report
      2016 Research-status Report
  • [Journal Article] 白血病に対する新しい薬物・細胞治療.2017

    • Author(s)
      今井千速
    • Journal Title

      日本医師会雑誌.

      Volume: 145 Pages: 2600-2604

    • Related Report
      2016 Research-status Report
  • [Journal Article] All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia.2016

    • Author(s)
      Yoshida T, Mihara K, Takei Y, Yanagihara K, Kubo T, Bhattacharyya J, Imai C, Mino T, Takihara Y, Ichinohe T.
    • Journal Title

      Clin Trans Immunol

      Volume: 5 Issue: 12

    • DOI

      10.1038/cti.2016.73

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan2016

    • Author(s)
      Imamura T, Kiyokawa N, Kato M, Imai C, Okamoto Y, Yano M, Ohki K, Yamashita Y, Kodama Y, Saito A, Mori M, Ishimaru S, Deguchi T, Hashii Y, Shimomura Y, Hori T, Kato K, Goto H, Ogawa C, Koh K, Taki T, Manabe A, Sato A, Kikuta A, Adachi S, Horibe K, Ohara A, Watanabe A, Kawano Y, Ishii E, Shimada H
    • Journal Title

      Blood Cancer J

      Volume: 6 Issue: 5 Pages: e419-e419

    • DOI

      10.1038/bcj.2016.28

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature.2016

    • Author(s)
      Sarashina T, Iwabuchi H, Miyagawa N, Sekimizu M, Yokosuka T, Fukuda K, Hamanoue S, Iwasaki F, Goto S, Shiomi M, Imai C, Goto H.
    • Journal Title

      Int J Hematol

      Volume: 104 Issue: 1 Pages: 139-143

    • DOI

      10.1007/s12185-016-1971-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia2016

    • Author(s)
      Nakazawa Y, Matsuda K, Kurata T, Sueki A, Tanaka M, Sakashita K, Imai C, Wilson MH, Koike K
    • Journal Title

      J Hematol Oncol

      Volume: 9 Issue: 1 Pages: 27-27

    • DOI

      10.1186/s13045-016-0256-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 小児造血器腫瘍における最新の話題2019

    • Author(s)
      今井千速
    • Organizer
      九州・山口小児がんフォーラム2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 小児固形腫瘍に対するCAR-T 療法の開発2018

    • Author(s)
      今井千速
    • Organizer
      第14 回北関東小児がんセミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] キメラ抗原受容体(CAR)による遺伝子改変T細胞療法 -肉腫への応用に向けて -Chimeric antigen receptor (CAR) gene-modified T cell therapy: Towards treatment of sarcoma2018

    • Author(s)
      今井千速
    • Organizer
      第91回日本整形外科学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] NKp44キメラ抗原受容体による新しいがん免疫治療の開発2018

    • Author(s)
      笠原靖史、久保暢大、申将守、高地貴行、岩渕晴子、今村勝、今井千速
    • Organizer
      第228回日本小児科学会新潟地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of CAR-T therapy using NKp44 ectodomain for antigen recognition2018

    • Author(s)
      笠原靖史、久保暢大、申将守、岩渕晴子、今村勝、今井千速
    • Organizer
      第10回血液疾患免疫療法学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Superior Activity of NKp44-CAR-T Cells in Comparison with Ex Vivo Expanded Activated NK cells or NKp30-CAR-T cells2018

    • Author(s)
      笠原靖史、申将守、久保暢大、岩渕晴子、今村勝、齋藤昭彦、今井千速
    • Organizer
      第60回日本小児血液・がん学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of novel chimeric antigen receptor targeting PD-1 ligands in cancer cells.2018

    • Author(s)
      Chansu Shin, Nobuhiro Kubo, Yasushi Kasahara, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PD-1 ligands are upregulated after T-cell attack in childhood solid tumors and may become a candidate for CAR-T cell therapy.2018

    • Author(s)
      Chansu Shin, Nobuhiro Kubo, Yasushi Kasahara, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai
    • Organizer
      第60回日本小児血液・がん学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of novel chimeric antigen receptor targeting PD-1 ligands in Osteosarcoma.2018

    • Author(s)
      Chansu Shin, Nobuhiro Kubo, Yasushi Kasahara, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai
    • Organizer
      50th annual congress of the international society of paediatric oncology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characteristics and Outcomes of Childhood ALL with ETV6-RUNX1: The CCLSG ALL 2004 Study.2017

    • Author(s)
      Imai, Chihaya
    • Organizer
      The 59th annual meeting of Japanese Society of Pediatric Hematology and Oncology
    • Related Report
      2017 Research-status Report
  • [Presentation] 新潟県における小児専門医療施設を考える:小児科医の立場から2017

    • Author(s)
      今井千速.
    • Organizer
      第721回新潟医学会シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] キメラ抗原受容体(CAR)の開発:白血病から固形がんへ2016

    • Author(s)
      今井千速
    • Organizer
      小児血液・がんセミナーin Chiba
    • Place of Presentation
      京葉銀行プラザ(千葉県千葉市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] キメラ抗原受容体(CAR):人工受容体遺伝子を導入したリンパ球による新たながん治療2016

    • Author(s)
      今井千速
    • Organizer
      第716回新潟医学会
    • Place of Presentation
      有壬会館(新潟県新潟市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] キメラ抗原受容体2018

    • Inventor(s)
      今井千速、笠原靖史
    • Industrial Property Rights Holder
      新潟大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-047242
    • Filing Date
      2018
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] キメラ抗原受容体2016

    • Inventor(s)
      今井千速、笠原靖史
    • Industrial Property Rights Holder
      今井千速、笠原靖史
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-182078
    • Filing Date
      2016-09-16
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2021-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi