Blood Transfusion Research Today is a free monthly online journal that collates and summarizes the latest research about Blood Transfusion, including details on blood donation, blood types, leukemia.

UTY-specific TCR-transfer generates potential graft-versus-leukaemia effector T cells.

Ivanov R, Hol S, Aarts T, Hagenbeek A, Slager EH, Ebeling S

Jordan Laboratory for Haemato-Oncology, Department of Haematology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.

Immunotherapeutic approaches that target antigens that are differentially recognized on haematopoietic and non-haematopoietic cells may specifically enhance the graft-versus-leukaemia (GVL) effect of donor lymphocyte infusion. In this study, we have characterized a new HLA-B*5201-restricted epitope of the UTY gene. Unusually, presentation of this epitope was restricted to lymphoblasts. As a result, a T cell clone specific to this epitope recognized normal and malignant male B and T lymphoblasts, while showing little reactivity towards male HLA-B*5201+ fibroblasts. Transfer of its T cell receptor (TCR) into donor T cells led to the generation of large numbers of T cells, which acquired the specificity of the original clone, its avidity and the differential pattern of reactivity towards lymphoblasts and fibroblasts. Remarkably, the specific response of TCR-transferred T cells was significantly higher than that of the original clone. This is the first demonstration of the possibility to preserve the specific pattern of a T cell response to a differentially expressed antigen after TCR-transfer and to augment the amplitude of this response concomitantly. These results indicate that it may be feasible to enhance the GVL effect of donor lymphocyte infusions in lymphoproliferative malignancies by the transfer of TCRs specific to epitopes that are differentially recognized on lymphoblasts.

Published 21 April 2005 in Br J Haematol, 129(3): 392-402.
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