Redifferentiation culture to generate helper T cells from iPS cells

• Project/Area Number: 18K15278
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyoto University
• Principal Investigator: Yohei Kawai 京都大学, iPS細胞研究所, 特定研究員 (90623364)
• 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: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: iPSC / T cell / immunotherapy / helper T cell / iPS細胞 / 免疫療法 / T細胞 / フィーダーフリー / 他家移植 / 棚卸 / 免疫細胞療法 / ヘルパーT細胞 / 細胞傷害性T細胞 / 再分化

Outline of Final Research Achievements

In this study we generated highly proliferative cytotoxic T lymphocytes (CTLs) from induced pluripotent stem cells (iPSCs) in complete feeder-free condition.
Specifically, we found cytokine combination of IL-7+IL-21 was beneficial in T-cell development culture while combination of IL-7+IL-15+IL-12+IL-18 was beneficial in T-cell expansion culture.

Academic Significance and Societal Importance of the Research Achievements

近年腫瘍や慢性難治感染症の治療法として注目を集めているT細胞免疫療法では輸注T細胞を疲弊させることなく大量に調製する事が必須条件となっている。本研究では高増殖性形質をiPSC由来T細胞に付与させることにより、分化と拡大培養を組み合わせて1ディッシュのiPSCから10^15個以上のT細胞作製を可能にした。この成果により既製品T細胞を患者に他家移植する画期的な棚卸式免疫療法が可能になると期待される

Research Products

• [Journal Article] Redifferentiation of Adaptive Na?ve-Like CTL from T-Cell-Derived iPSC (2019)
  • Author(s): Kawai Yohei、Kaneko Shin
  • Journal Title: Methods Mol Biol Volume: 2048 Pages: 71-75
  • DOI: 10.1007/978-1-4939-9728-2_7
  • ISBN: 9781493997275, 9781493997282
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] iPSC-derived T cells exhibit superior effector functionality with rejuvenated phenotype compared to parental T-cell clone (2018)
  • Author(s): 河合洋平
  • Organizer: 血液疾患免疫療法学会
• [Presentation] iPSC-derived T cells exhibit superior effector function with rejuvenated phenotype compared to parental T-cell clone (2018)
  • Author(s): 河合洋平
  • Organizer: 免疫学会
• [Patent(Industrial Property Rights)] CD3陽性細胞の拡大培養方法 (2018)
  • Inventor(s): 金子新、河合洋平、有馬寿来留、葛西義明、林哲、滝口麻衣子
  • Industrial Property Rights Holder: 金子新、河合洋平、有馬寿来留、葛西義明、林哲、滝口麻衣子
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Acquisition Date: 2018
• [Patent(Industrial Property Rights)] メモリーT細胞の増殖を亢進する方法 (2018)
  • Inventor(s): 金子新、河合洋平、高柳晋一郎、國里篤志、中願寺風香、福本健
  • Industrial Property Rights Holder: 金子新、河合洋平、高柳晋一郎、國里篤志、中願寺風香、福本健
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Acquisition Date: 2018