title: 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.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: James
authors.initials: J
authors.lastname: Ferrara
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny