Development of in vitro culture to generate helper T cells from iPS cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07694
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyoto University
• Principal Investigator: Kawai Yohei 京都大学, iPS細胞研究所, 特定助教 (90623364)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: helper T cell / iPS cell / Tumor immunotherapy

Outline of Final Research Achievements

We have developed in vitro culture system which can generate helper T cells from iPS cells in complete feeder-free condition. We found iPS cell-derived helper T cells expressed helper-associated transcription factor Thpok abundantly and induced expression of a central helper effector molecule CD40L, which is involved in dendritic cell maturation, equivalently or more compared with primary helper T cells.
Furthermore, we found the iPS cell-derived helper T cells could acquire cytotoxic activity during specific cell expansion culture. This cytotoxic helper T cells showed potent anti-tumor activity with superior cytokine production and proliferation capacity compared with conventional iPS cell-derived killer T cells.

Free Research Field

Tumor immunotherapy

Academic Significance and Societal Importance of the Research Achievements

腫瘍免疫治療においては腫瘍抗原の発現低下による免疫回避や免疫抑制的な腫瘍微小環境の修正が重要であるが、この問題の解決にはヘルパーT細胞が重要な役割を果たし得る。本件で作製されたiPS細胞由来ヘルパーT細胞はヘルパーT細胞としての機能に加え、①フィーダーフリーで作製できるため臨床応用に対応しやすい、iPS細胞をセルソースとしているため②大量生産が可能、③ゲノム編集が容易、④品質管理が容易という強みも併せ持つ。さらにシンプルな操作でフィーダーフリー条件でiPSCから簡便にヘルパーT細胞を誘導できるため、本研究で樹立された分化培養系は、サンプルの入手が困難なヒトT細胞分化研究にも貢献し得ると考える。