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Augmentation of virus-specific immunity after hematopoietic stem cell transplantation by adoptive T-Cell therapy

Peggs, KS; Mackinnon, S; (2004) Augmentation of virus-specific immunity after hematopoietic stem cell transplantation by adoptive T-Cell therapy. HUM IMMUNOL , 65 (5) 550 - 557. 10.1016/j.humimm.2004.02.016.

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Abstract

Adoptive transfer of virus-specific T cells offers the potential for accelerating reconstitution of antigen-specific immunity after allogeneic hematopoietic stem cell transplantation. However, the logistics of producing virus-specific T cells and the risk of inducing graft-versus-host disease has limited their application. We developed a relatively simple system employing cytomegalovirus lysate-pulsed, monocyte-derived dendritic cells as stimulator cells, requiring only a single blood draw from the donor. We treated 16 patients with these T-cell lines, administered after the detection of human cytomegalovirus (HCMV) DNA by polymerase chain reaction. Massive in vivo expansions of HCMV-specific cytotoxic T lymphocytes (3-5 log) were observed within days of adoptive transfer. In eight cases viral titers were decreasing within 5 days and antiviral drug therapy was not required. The T-cell receptor CDR3 lengths of HCMV-specific cytotoxic T lymphocytes expanding in vivo were identical to those of the transferred cells. A low incidence of late CMV reactivation was seen (2/14 assessable patients compared with 45/72 historical controls, p = 0.001) and no significant toxicities were observed. Our findings indicate that application of cell lines generated in relatively short-term in vitro cultures is both feasible and effective in a clinical environment. This simple in vitro methodology should allow widespread application of adoptive transfer of virus-specific T cells. Human Immunology 65, 550-557 (2004). (C) American Society for Histocompatibility and Immunogenetics, 2004. Published by Elsevier Inc.

Type: Article
Title: Augmentation of virus-specific immunity after hematopoietic stem cell transplantation by adoptive T-Cell therapy
DOI: 10.1016/j.humimm.2004.02.016
Keywords: hematopoietic stem cell transplantation, cytomegalovirus, adoptive cellular therapy, DENDRITIC CELLS, CYTOMEGALOVIRUS-INFECTION, CMV INFECTION, RECONSTITUTION, ANTIGEN, RECIPIENTS, RESPONSES, CLONES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/171867
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