Regeneration of Human Tumor Antigen-Specific T Cells from iPSCs Derived from Mature CD8+ T Cells
Menée in vitro, cette étude présente une méthode permettant, à l'aide de cellules souches pluripotentes induites, d'engendrer des lymphocytes T spécifiques d'un antigène tumoral, l'épitope MART1 associé au mélanome
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 TCR²+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 IFN³, 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.
º iPSCs generated from T cells specific for the MART-1 melanoma epitope
º Differentiation of iPSCs into T cells with a MART-1 specific T cell receptor
º MART-1-based stimulation of T cells demonstrates retained antigen specificity
T cells specific for a tumor antigen made via iPSCs and reprogramming illustrate a potential future approach to cancer immunotherapy.
Cell stem cell , résumé, 2012