論文

国際誌
2020年12月11日

Regeneration of Tumor-Antigen-Specific Cytotoxic T Lymphocytes from iPSCs Transduced with Exogenous TCR Genes.

Molecular therapy. Methods & clinical development
  • Takuya Maeda
  • Seiji Nagano
  • Soki Kashima
  • Koji Terada
  • Yasutoshi Agata
  • Hiroshi Ichise
  • Manami Ohtaka
  • Mahito Nakanishi
  • Fumihiro Fujiki
  • Haruo Sugiyama
  • Toshio Kitawaki
  • Norimitsu Kadowaki
  • Akifumi Takaori-Kondo
  • Kyoko Masuda
  • Hiroshi Kawamoto
  • 全て表示

19
開始ページ
250
終了ページ
260
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.omtm.2020.09.011

In the current adoptive T cell therapy, T cells from a patient are given back to that patient after ex vivo activation, expansion, or genetic manipulation. However, such strategy depends on the quality of the patient's T cells, sometimes leading to treatment failure. It would therefore be ideal to use allogeneic T cells as "off-the-shelf" T cells. To this aim, we have been developing a strategy where potent tumor-antigen-specific cytotoxic T lymphocytes (CTLs) are regenerated from T-cell-derived induced pluripotent stem cells (T-iPSCs). However, certain issues still remain that make it difficult to establish highly potent T-iPSCs: poor reprogramming efficiency of T cells into iPSCs and high variability in the differentiation capability of each T-iPSC clone. To expand the versatility of this approach, we thought of a method to produce iPSCs equivalent to T-iPSCs, namely, iPSCs transduced with exogenous T cell receptor (TCR) genes (TCR-iPSCs). To test this idea, we first cloned TCR genes from WT1-specific CTLs regenerated from T-iPSCs and then established WT1-TCR-iPSCs. We show that the regenerated CTLs from TCR-iPSCs exerted cytotoxic activity comparable to those from T-iPSCs against WT1 peptide-loaded cell line in in vitro model. These results collectively demonstrate the feasibility of the TCR-iPSC strategy.

リンク情報
DOI
https://doi.org/10.1016/j.omtm.2020.09.011
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33102617
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566080
ID情報
  • DOI : 10.1016/j.omtm.2020.09.011
  • PubMed ID : 33102617
  • PubMed Central 記事ID : PMC7566080

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