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Nat Med. 2010 May;16(5):565-70, 1p following 570. doi: 10.1038/nm.2128. Epub 2010 Apr 18.

Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy.

Author information

1
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. g.bendle@nki.nl

Abstract

The transfer of T cell receptor (TCR) genes can be used to induce immune reactivity toward defined antigens to which endogenous T cells are insufficiently reactive. This approach, which is called TCR gene therapy, is being developed to target tumors and pathogens, and its clinical testing has commenced in patients with cancer. In this study we show that lethal cytokine-driven autoimmune pathology can occur in mouse models of TCR gene therapy under conditions that closely mimic the clinical setting. We show that the pairing of introduced and endogenous TCR chains in TCR gene-modified T cells leads to the formation of self-reactive TCRs that are responsible for the observed autoimmunity. Furthermore, we demonstrate that adjustments in the design of gene therapy vectors and target T cell populations can be used to reduce the risk of TCR gene therapy-induced autoimmune pathology.

PMID:
20400962
DOI:
10.1038/nm.2128
[Indexed for MEDLINE]

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