Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8+ T cells

Raul Vizcardo, Kyoko Masuda, Daisuke Yamada, Tomokatsu Ikawa, Kanako Shimizu, Shin Ichiro Fujii, Haruhiko Koseki, Hiroshi Kawamoto

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)

Abstract

Antigen-specific T cells represent a potential therapeutic avenue for a variety of conditions, but current approaches for generating such cells for therapeutic purposes are limited. In this study, we established iPSCs from mature cytotoxic T cells specific for the melanoma epitope MART-1. When cocultured with OP9/DLL1 cells, these iPSCs efficiently generated TCRβ+CD4+CD8+ double positive (DP) cells expressing a T cell receptor (TCR) specific for the MART-1 epitope. Stimulation of these DP cells with anti-CD3 antibody generated a large number of CD8 + T cells, and more than 90% of the resulting cells were specific for the original MART-1 epitope. Stimulation of the CD8+ T cells with MART-1 antigen-presenting cells led to the secretion of IFNγ, demonstrating their specific reactivity. The present study therefore illustrates an approach for cloning and expanding functional antigen-specific CD8 + T cells that might be applicable in cell-based therapy of cancer.

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalCell Stem Cell
Volume12
Issue number1
DOIs
Publication statusPublished - 03-01-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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