title: Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells.
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.
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
authors.forename: Raul
authors.initials: R
authors.lastname: Vizcardo
authors.forename: Kyoko
authors.initials: K
authors.lastname: Masuda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Ikawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimizu
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Fujii
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D058965:MART-1 Antigen / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000378:metabolism*
chemical_list: D058965:MART-1 Antigen