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Drug discovery research on tumor vessels-insuring CAR-T cells aimed at establishing a new generation treatment for sarcoma

Research Project

Project/Area Number 18H04018
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionOsaka University

Principal Investigator

OKADA Naoki  大阪大学, 薬学研究科, 教授 (90312123)

Co-Investigator(Kenkyū-buntansha) 岡田 潔  大阪大学, 医学系研究科, 特任准教授 (40576279)
竹中 聡  大阪大学, 医学系研究科, 助教 (00588379)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2019: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Keywords細胞療法 / 腫瘍免疫 / キメラ抗原受容体 / 肉腫 / 血管新生
Outline of Final Research Achievements

Soft tissue sarcomas (STSs) are heterogeneous and aggressive malignancies with few effective therapies available. We have developed T cells expressing a vascular endothelial growth factor receptor 2 (VEGFR2)-specific chimeric antigen receptor (CAR) to establish tumor vessels-injuring CAR-T cell therapy. In this study, we optimized the manufacturing and transportation of mRNA-transfected anti-VEGFR2 CAR-T cells and collected information that allowed the extrapolation of efficacy and safety potential of our therapy for STS patients. Importantly, immunohistochemistry showed that most of the STS patients’ specimens expressed VEGFR2, suggesting a great potential of our approach as a new treatment option for STSs.

Academic Significance and Societal Importance of the Research Achievements

従来の低分子医薬や抗体医薬では難しかった「腫瘍血管傷害」を作用機序とするCAR-T細胞の再生医療等製品が実用化されれば、固形がんに対して汎用性に優れる新規がん治療オプションを創出することとなり、集学的治療戦略に組み込むことで難治性がんに対する奏効率の向上に大きく貢献できるものと期待している。

Report

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

    (29 results)

All 2021 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (23 results)

  • [Journal Article] Structure of the Signal Transduction Domain in Second-Generation CAR Regulates the Input Efficiency of CAR Signals2021

    • Author(s)
      Fujiwara Kento、Kitaura Masaki、Tsunei Ayaka、Kusabuka Hotaka、Ogaki Erika、Okada Naoki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 5 Pages: 2476-2476

    • DOI

      10.3390/ijms22052476

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients2020

    • Author(s)
      Fujiwara Kento、Sasawatari Shigemi、Nakai Sho、Imaeda Keisuke、Nagai Seina、Matsuno Yoshihiro、Hatanaka Kanako、Hatanaka Yutaka、Takenaka Satoshi、Okada Naoki
    • Journal Title

      Cancers

      Volume: 12 Issue: 10 Pages: 2735-2735

    • DOI

      10.3390/cancers12102735

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development and functional analysis of an anticancer T‐cell medicine with immune checkpoint inhibitory ability2020

    • Author(s)
      Fujiwara Kento、Shigematsu Kazuki、Tachibana Masashi、Okada Naoki
    • Journal Title

      IUBMB Life

      Volume: 72 Issue: 8 Pages: 1649-1658

    • DOI

      10.1002/iub.2280

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of scFv structure in chimeric antigen receptor on receptor expression efficiency and antigen recognition properties2020

    • Author(s)
      Fujiwara Kento、Masutani Mizuki、Tachibana Masashi、Okada Naoki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 527 Issue: 2 Pages: 350-357

    • DOI

      10.1016/j.bbrc.2020.03.071

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold2020

    • Author(s)
      Fujiwara Kento、Tsunei Ayaka、Kusabuka Hotaka、Ogaki Erika、Tachibana Masashi、Okada Naoki
    • Journal Title

      Cells

      Volume: 9 Issue: 5 Pages: 1182-1182

    • DOI

      10.3390/cells9051182

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 遺伝子改変T細胞療法の開発状況2018

    • Author(s)
      藤原健人, 岡田直貴
    • Journal Title

      PHARMSTAGE

      Volume: 18 Pages: 32-36

    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗原親和性の異なる抗Robo4 CAR-T細胞間での抗腫瘍効果の比較2021

    • Author(s)
      長井聖奈, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 軟部肉腫に対する腫瘍血管障害性CAR-T細胞療法の奏功予測研究2020

    • Author(s)
      中井 翔, 藤原健人, 今枝啓輔, 長井聖奈, 安田直弘, 前 裕和, 王谷英達, 濱田健一郎, 岡田直貴, 竹中 聡
    • Organizer
      第53回日本整形外科学会 骨・軟部腫瘍学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 固形がんに対する抗Robo4 CAR-T細胞療法の開発に向けた基礎的検討2020

    • Author(s)
      長井聖奈, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 軟部肉腫に対する腫瘍血管傷害性CAR-T細胞療法の有効性・安全性予測に関する検討2020

    • Author(s)
      藤原健人, 中井 翔, 安田直弘, 王谷英達, 濱田健一郎, 竹中 聡, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 固形がんに対するCAR-T細胞療法におけるROBO4標的化の有用性評価とROBO4特異的CARの構築2020

    • Author(s)
      長井聖奈, 藤原健人, 福井麻琴, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] キメラ抗原受容体 (CAR) が受ける翻訳後修飾のCAR-T細胞機能への影響2020

    • Author(s)
      今枝啓輔, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Research to predict the effectiveness of tumor vessel-injuring CAR-T cell therapy for soft tissue sarcoma2019

    • Author(s)
      Kento Fujiwara, Sho Nakai, Naohiro Yasuda, Hidetatsu Otani, Kenichiro Hamada, Satoshi Takenaka, Masashi Tachibana, Naoki Okada
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CARの細胞外領域に適したscFv構築法の確立に向けた基礎的検討2019

    • Author(s)
      藤原健人, 升谷美月, 立花雅史, 岡田直貴
    • Organizer
      第23回日本がん免疫学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] キメラ抗原受容体のscFv構造と膜発現強度との連関解析2019

    • Author(s)
      藤原健人, 升谷美月, 立花雅史, 岡田直貴
    • Organizer
      第19回日本蛋白質科学会年会/第71回日本細胞生物学会大会 合同年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ファージライブラリ由来scFv cloneを用いたキメラ抗原受容体の構造最適化検討2019

    • Author(s)
      升谷美月, 藤原健人, 鎌田春彦, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗VEGFR2 CAR-T細胞療法のin vitro安全性・有効性評価系の構築2019

    • Author(s)
      我喜屋良行, 藤原健人, 竹中 聡, 濱田健一郎, 王谷英達, 中井 翔, 安田直弘, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CAR-T細胞機能に及ぼすCAR翻訳後修飾の影響2019

    • Author(s)
      今枝啓輔, 藤原健人, 鎌田春彦, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PD-L1/PD-1シグナル阻害能を付与した抗がんT細胞医薬の創製と機能解析2019

    • Author(s)
      重松知樹, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CARのシグナル伝達領域改変によるCAR-T細胞機能制御に関する基礎的検討2019

    • Author(s)
      北裏将樹, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 腫瘍血管傷害型CAR-T細胞医薬の品質・性能規格化に向けた基礎的検討2019

    • Author(s)
      藤原健人, 我喜屋良行, 笹渡繁巳, 神垣 隆, 立花雅史, 岡田直貴
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肉腫に対する腫瘍血管傷害型CAR-T細胞療法の開発2019

    • Author(s)
      我喜屋良行, 藤原健人, 富山 舞, 笹渡繁巳, 竹中 聡, 神垣 隆, 岡田直貴
    • Organizer
      第16回日本免疫治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Creation of T cell medicine capable of avoiding functional depression due to PD-L1/PD-1 signaling2018

    • Author(s)
      Kazuki Shigematsu, Kento Fujiwara, Masashi Tachibana, Naoki Okada
    • Organizer
      第47回日本免疫学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Structure-activity correlation analysis by using 2nd-generation CARs with modified of signal transduction domain2018

    • Author(s)
      Masaki Kitaura, Kento Fujiwara, Masashi Tachibana, Naoki Okada
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Structure-activity correlation analysis by using 1st-generation CARs with modified of hinge/transmembrane domain2018

    • Author(s)
      Kento Fujiwara, Masashi Tachibana, Naoki Okada
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞内シグナル伝達領域を改変した各種第二世代CARのT細胞における発現・機能比較2018

    • Author(s)
      北裏将樹, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒンジ・膜貫通領域を改変した各種第一世代CARのT細胞における発現・機能比較2018

    • Author(s)
      藤原健人, 今枝啓輔, 立花雅史, 岡田直貴
    • Organizer
      第22回日本がん免疫学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 各種構造改変キメラ抗原受容体のT細胞膜上での存在状態に関する検討2018

    • Author(s)
      今枝啓輔, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PD-L1/PD- 1シグナルによる機能不全を回避できるT細胞医薬の創製と機能解析2018

    • Author(s)
      重松知樹, 藤原健人, 立花雅史, 岡田直貴
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report

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

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