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Comment
. 2010 Nov;2(6):791-4.
doi: 10.2217/imt.10.73.

Immunotherapy through T-cell receptor gene transfer induces severe graft-versus-host disease

James Ferrara  1 , Pavan Reddy, Sophie Paczesny
Affiliations
Comment

Immunotherapy through T-cell receptor gene transfer induces severe graft-versus-host disease

James Ferrara et al. Immunotherapy. 2010 Nov.

Abstract

Evaluation of: Bendle GM, Linnemann C, Hooijkaas AI et al.: Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat. Med. 16(5), 565-570 (2010). Graft-versus-host disease is commonly associated with allogeneic hematopoietic cell transplantation, as it is the major complication. This article reports that, after immunotherapy with lymphocytes that have been transduced with T-cell receptor (TCR) genes of known specificity, graft-versus-host disease can occur through TCR gene transfer. This autoimmune pathology occurs through the formation of self-reactive TCRs as a result of one chain of the transduced TCR cross-pairing with an endogenous TCR. Certain adjustments in the design of gene therapy vectors may help reduce the risk of such autoimmune phenomena.

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Figures

Figure 1
Figure 1. Each T lymphocyte expresses, on their surface, numerous T-cell receptors, each composed of [alpha] and [beta] chains
The tumor-specific T cells have been generated by the transfer of transgenic T-cell receptors (TCRs). Rarely, a T cell that received an [alpha]- or [beta]-chain of the endogenous T cells that have cross-paired with the [alpha]- or [beta]-chain of the transgenic TCR will become self-reactive and provoke the TCR gene TI-GVHD pathology. TI-GVHD: Transfer-induced graft-versus-host disease.
See this image and copyright information in PMC

Comment on

References

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