論文

査読有り 国際誌
2020年3月13日

High Frequency Production of T Cell-Derived iPSC Clones Capable of Generating Potent Cytotoxic T Cells.

Molecular therapy. Methods & clinical development
  • Seiji Nagano
  • ,
  • Takuya Maeda
  • ,
  • Hiroshi Ichise
  • ,
  • Soki Kashima
  • ,
  • Manami Ohtaka
  • ,
  • Mahito Nakanishi
  • ,
  • Toshio Kitawaki
  • ,
  • Norimitsu Kadowaki
  • ,
  • Akifumi Takaori-Kondo
  • ,
  • Kyoko Masuda
  • ,
  • Hiroshi Kawamoto

16
開始ページ
126
終了ページ
135
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.omtm.2019.12.006

Current adoptive T cell therapies conducted in an autologous setting are costly, time-consuming, and depend on the quality of the patient's T cells, and thus it would be highly beneficial to develop an allogeneic strategy. To this aim, we have developed a method by which cytotoxic T lymphocytes (CTLs) are regenerated from induced pluripotent stem cells that are originally derived from T cells (T-iPSCs). In order to assess the feasibility of this strategy, we investigated the frequency of usable T-iPSC clones in terms of their T cell-generating capability and T cell receptor (TCR) affinity. We first established eight clones of T-iPSCs bearing different MART-1-specific TCRs from a healthy volunteer. Whereas all clones were able to give rise to mature CTLs, cell yield varied greatly, and five clones were considered to be usable. TCR affinity in the regenerated CTLs showed a large variance among the eight clones, but functional avidities measured by cytotoxic activity were almost equivalent among three selected clones representing high, medium, and low TCR affinity. In a total of 50 alloreactivity tests using five CTL clones versus ten target cells, alloreactivity was seen in only three cases. These findings collectively support the feasibility of this T-iPSC strategy.

リンク情報
DOI
https://doi.org/10.1016/j.omtm.2019.12.006
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31970197
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965501

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