Regeneration of CD8αβ T cells from T-cell-derived iPSC imparts potent tumor antigen-specific cytotoxicity

Takuya Maeda, Seiji Nagano, Hiroshi Ichise, Keisuke Kataoka, Daisuke Yamada, Seishi Ogawa, Haruhiko Koseki, Toshio Kitawaki, Norimitsu Kadowaki, Akifumi Takaori-Kondo, Kyoko Masuda, Hiroshi Kawamoto

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


Although adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising cancer therapeutic direction, the generation of antigen-specific CTL from patients has faced difficulty in efficient expansion in ex vivo culture. To resolve this issue, several groups have proposed that induced pluripotent stem cell technology be applied for the expansion of antigen-specific CTL, which retain expression of the same T-cell receptor as original CTL. However, in these previous studies, the regenerated CTL are mostly of the CD8αα+ innate type and have less antigen-specific cytotoxic activity than primary CTL. Here we report that, by stimulating purified iPSC-derived CD4/CD8 double-positive cells with anti-CD3 antibody, T cells expressing CD8αβ were generated and exhibited improved antigen-specific cytotoxicity compared with CD8αα+ CTL. Failure of CD8αβ T-cell production using the previous method was found to be due to killing of double-positive cells by the double-negative cells in the mixed cultures. We found that WT1 tumor antigen-specific CTL regenerated by this method prolonged the survival of mice bearing WT1-expressing leukemic cells. Implementation of our methods may offer a useful clinical tool.

Original languageEnglish
Pages (from-to)6839-6850
Number of pages12
JournalCancer Research
Issue number23
Publication statusPublished - 01-12-2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'Regeneration of CD8αβ T cells from T-cell-derived iPSC imparts potent tumor antigen-specific cytotoxicity'. Together they form a unique fingerprint.

Cite this