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

James Ferrara, Pavan Reddy, Sophie Paczesny

Research output: Contribution to journalComment/debate

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)791-794
Number of pages4
Issue number6
StatePublished - Nov 2010
Externally publishedYes


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


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