Novel chimeric antigen receptor modified T cells against IGF receptor for osteosarcoma

• Project/Area Number: 15K09648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Nagoya University
• Principal Investigator: NIshio Nobuhiro 名古屋大学, 医学部附属病院, 特任助教 (00586430)
• Co-Investigator(Kenkyū-buntansha): 中沢 洋三 信州大学, 医学部, 助教 (60397312)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: キメラ抗原受容体 / 骨肉腫

Outline of Final Research Achievements

Genetically modified T cell therapy using chimeric antigen receptor (CAR) (CAR - T therapy) has been shown to be promising as a new cancer treatment method, and application to various cancers is expected. In this study, we developed a piggyBac transposon vector for novel chimeric antigen receptor genetically modified T cells for the antigen expressed on osteosarcoma cells and our culture method enabling high transduction efficiency using the piggyBac transposon gene transfer method. The novel CAR-T cells in this study exerted potent killing activity against osteosarcoma cells. Based on this study, we could obtain baseline data of novel immunotherapy for osteosarcoma.

Research Products

• [Journal Article] Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in piggyBac Transposon-Engineered T Cells (2018)
  • Author(s): Morita Daisuke、Nishio Nobuhiro、Saito Shoji、Tanaka Miyuki、Kawashima Nozomu、Okuno Yusuke、Suzuki Satoshi、Matsuda Kazuyuki、Maeda Yasuhiro、Wilson Matthew H.、Dotti Gianpietro、Rooney Cliona M.、Takahashi Yoshiyuki、Nakazawa Yozo
  • Journal Title: Molecular Therapy - Methods & Clinical Development Volume: 8 Pages: 131-140
  • DOI: 10.1016/j.omtm.2017.12.003
  • Peer Reviewed / Int'l Joint Research
• [Presentation] CAR-T cell in Leukemia (2017)
  • Author(s): Nobuhiro Nishio
  • Organizer: Precision Oncology: Genomics Data from Thai patients vs. Global Counterparts
  • Place of Presentation: バンコク、タイ
  • Year and Date: 2017-03-02
  • Invited
• [Presentation] PiggyBac遺伝子改変CD19キメラ抗原受容体T細胞療法のFirst in Human試験にむけた基盤研究 (2017)
  • Author(s): 西尾信博、鈴木哲、奥野友介、中沢洋三、田中美幸、盛田大介、濱田太立、川島希、成田敦、村松秀城、濱麻人、小島勢二、高橋義行
  • Organizer: 第６回日本血液学会東海地方会
• [Presentation] PiggyBac Mediated T cells Expressing anti CD19 Chimeric Antigen Receptor for a Clinical Trial (2017)
  • Author(s): Nobuhiro Nishio, Yozo Nakazawa, Motoharu Hamada, Satoshi Suzuki, Miyuki Takana, Daisuke Morita, Nozomu Kawashima, Yusuke Okuno, Atsushi Narita, Asahito Hama, Hideki Muramatsu, Wilson H. Matthew, Cliona M. Rooney, Gianpietro Dotti, Seiji Kojima, Yoshiyuki Takahashi
  • Organizer: 第20回American Society of Gene and Cell Therapy
  • Int'l Joint Research
• [Presentation] PiggyBac Mediated T cells Expressing Anti-CD19 Chimeric Antigen Receptor for a Clinical Trial (2017)
  • Author(s): Nobuhiro Nishio, Yozo Nakazawa, Motoharu Hamada, Satoshi Suzuki, Miyuki Takana, Daisuke Morita, Nozomu Kawashima, Yusuke Okuno, Atsushi Narita, Asahito Hama, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi
  • Organizer: 第8回日本血液学会国際シンポジウム
  • Int'l Joint Research
• [Presentation] Durable Remission After Salvage Chemotherapy with Combining Bortezomib and Vorinostat Followed by CD19 CAR-T Therapy in a Patient with MLL-rearranged ALL After Early Relapse Post Allogeneic Hematopoietic Stem Cell Transplantation (2017)
  • Author(s): Nobuhiro Nishio, Kai Wang, Shinsuke Kataoka, Kotaro Narita, Hironobu Kitazawa, et al.
  • Organizer: 第５９回米国血液学会
  • Int'l Joint Research
• [Presentation] Genome-wide Profile of Integration Sites of Chimeric Antigen Receptor (CAR) Gene in PiggyBac-modified Human T Cells. (2016)
  • Author(s): Motoharu Hamada, Yusuke Okuno, Nobuhiro Nishio, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Asahito Hama, Seiji Kojima, Yozo Nakazawa, and Yoshiyuki Takahashi
  • Organizer: 第58回日本小児血液・がん学会学術集会
  • Place of Presentation: 品川プリンスホテル（東京都品川区）
  • Year and Date: 2016-12-15
• [Presentation] PiggyBac mediated T cells expressing CD19 chimeric antigen receptor for a “first in human” clinical trial (2016)
  • Author(s): Nobuhiro Nishio, Yozo Nakazawa, Motoharu Hamada, Satoshi Suzuki, Miyuki Takana, Daisuke Morita, Nozomu Kawashima, Yusuke Okuno, Atsushi Narita, Asahito Hama, Hideki Muramatsu, Wilson H. Matthew, Cliona M. Rooney, Gianpietro Dotti, Seiji Kojima, Yoshiyuki Takahashi
  • Organizer: 第58回日本小児血液・がん学会学術集会
  • Place of Presentation: 品川プリンスホテル（東京都品川区）
  • Year and Date: 2016-12-15
• [Presentation] PiggyBac mediated CD19 chimeric antigen receptor modified T cells for a first in human clinical trial. (2016)
  • Author(s): Nobuhiro Nishio, Yozo Nakazawa, Motoharu Hamada, Satoshi Suzuki, Miyuki Takana, Daisuke Morita, Nozomu Kawashima, Yusuke Okuno, Atsushi Narita, Asahito Hama, Hideki Muramatsu, Wilson H. Matthew, Cliona M. Rooney, Gianpietro Dotti, Seiji Kojima, Yoshiyuki Takahashi.
  • 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: 2016-10-13
• [Presentation] Detection of Integration Sites of CD19 Chimeric Antigen Receptor Gene in a Non-viral Gene Transfer System. (2016)
  • Author(s): Motoharu Hamada, Yusuke Okuno, Nobuhiro Nishio, Matthew H. Wilson, Nozomu Kawashima, Atsushi Narita, Hideki Muramatsu, Asahito Hama, Seiji Kojima, Yozo Nakazawa, Yoshiyuki Takahashi.
  • Organizer: The 7th JSH 国際シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
  • Year and Date: 2016-05-13
• [Presentation] Detection of integration sites of CD19 chimeric antigen receptor gene in a non-viral gene transfer system. (2016)
  • Author(s): Motoharu Hamada, Yusuke Okuno, Nobuhiro Nishio, Matthew H. Wilson, Seiji Kojima, Yozo Nakazawa, and Yoshiyuki Takahashi
  • Organizer: American Society of Gene and Cell Therapy
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2016-05-04
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] キメラ抗原受容体を発現する遺伝子改変Ｔ細胞の調製方法 (2016)
  • Inventor(s): 西尾信博、中沢洋三、田中美幸、盛田大介、高橋義行
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-10-07
  • Overseas