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

Seiji Nagano, Takuya Maeda, Hiroshi Ichise, Soki Kashima, Manami Ohtaka, Mahito Nakanishi, Toshio Kitawaki, Norimitsu Kadowaki, Akifumi Takaori-Kondo, Kyoko Masuda, Hiroshi Kawamoto

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)126-135
Number of pages10
JournalMolecular Therapy - Methods and Clinical Development
Volume16
DOIs
Publication statusPublished - 13-03-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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