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Notch-mediated Conversion of Activated T Cells into Stem Cell Memory-like T Cells for Adoptive Immunotherapy

Overview
Journal Nat Commun
Specialty Biology
Date 2017 May 23
PMID 28530241
Citations 58
Authors
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Abstract

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8 T cells can be generated in vitro from naive CD8 T cells via Wnt signalling; however, methods do not yet exist for inducing T cells from activated or memory T cells. Here, we show a strategy for generating T-like cells in vitro (iT cells) from activated CD4 and CD8 T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iT cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.

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