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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)250-260
Number of pages11
JournalMolecular Therapy - Methods and Clinical Development
Volume19
DOIs
Publication statusPublished - 11-12-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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