Immunotherapy through T-Cell Receptor Gene Transfer Induces Severe Graft-Versus-Host Disease

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.

KEYWORDS::

• autoimmunity
• graft-versus-host disease
• immunotherapy
• mixed dimers
• TCR cross-pairing
• TCR gene therapy
• TCR gene transfer
• self-reactivity

Financial & competing interests disclosure

The authors have received NIH grants P01-CA039542-20 and RC1-HL-101102. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.