Development of a differentiation method to generate iPSC-derived T cell bank for allogeneic T-cell therapy

• Project/Area Number: 18K16085
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto University
• Principal Investigator: Iriguchi Shoichi 京都大学, iPS細胞研究所, 特定研究員 (50737442)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: iPS細胞 / T細胞 / T細胞免疫療法 / 他家移植 / 遺伝子改変T細胞療法 / 多能性幹細胞

Outline of Final Research Achievements

iPSC-based regenerative medicine hold promise for the future medicine and clinical trials testing the efficacy of iPSC-derived tissues are underway. T cells, a type of immune cells, can be generated from iPSCs. Preclinical studies have demonstrated the potential of iPSC-derived T cells to treat cancer and other immunological diseases. However, in order to initiate clinical trials, methods to generate T cells from iPSCs should be adopted to regulatory requirements. In this study, we have tested a number of culture conditions and materials and identified T cell generation methods suitable to clinical applications.

Academic Significance and Societal Importance of the Research Achievements

近年、遺伝子改変したT細胞を用いた新しい癌免疫療法が、特に血液がんで著名な効果をあげている。遺伝子改変T細胞を用いた免疫療法を広く普及させる為に、他人の細胞から遺伝子改変T細胞を予め作製しておき、必要なときにすぐに投与可能なT細胞製剤を開発する試みがなされている。iPS細胞から作製するT細胞はこの様な目的で使用するT細胞製剤の候補になると考えられる。本研究成果は今後のiPS細胞から作製したT細胞を臨床応用する上で基盤技術となる事から、遺伝子改変T細胞免疫療法の普及に貢献するものと思われる。

Research Products

• [Journal Article] Toward the development of true “off-the-shelf” synthetic T-cell immunotherapy (2019)
  • Author(s): Iriguchi Shoichi、Kaneko Shin
  • Journal Title: Cancer Science Volume: 110 Issue: 1 Pages: 16-22
  • DOI: 10.1111/cas.13892
  • NAID: 120006547385
  • Peer Reviewed / Open Access
• [Journal Article] Enhancing T cell Receptor Stability in Rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy (2018)
  • Author(s): Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S, Takiguchi M, Kassai Y, Imai E, Yasui Y, Kawai Y, Zhang R, Uemura Y, Miyoshi H, Nakanishi M, Watanabe A, Hayashi A, Kawana K, Fujii T, Nakatsura T, Kaneko S
  • Journal Title: Cell Stem Cell Volume: 23 Issue: 6 Pages: 850-858
  • DOI: 10.1016/j.stem.2018.10.005
  • Peer Reviewed / Open Access
• [Presentation] 同種他家T細胞免疫療法の臨床応用へ向けたiPS細胞由来T細胞製造方法の開発 (2020)
  • Author(s): 入口翔一、安井裕、河合洋平、有馬寿来留、國友美穂子、佐藤崇之、安川正貴、中面哲也、金子新
  • Organizer: 第17回日本免疫治療学会学術集会
• [Presentation] Characterization of prognitor T cells derived from human pluripotent stem cells under feeder-free conditions (2018)
  • Author(s): Shoichi Iriguchi, Tokuyuki Shinohara, Keiko Koga, Akira Hayashi, Yoshiaki Kassai, and Shin Kaneko
  • Organizer: ISSCR 2018 Annual Meeting
  • Int'l Joint Research