The Journal of Experimental Medicine
StemCell Technologies
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Published 1 August 2005. doi:10.1084/jem.20040613
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 3, 379-386
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BRIEF DEFINITIVE REPORT

 Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers

Mark Cobbold1, Naeem Khan1, Batoul Pourgheysari1, Sudhir Tauro2, Dorothy McDonald4, Husam Osman3, Mario Assenmacher5, Lucinda Billingham1, Colin Steward6, Charles Crawley7, Eduardo Olavarria7, John Goldman7, Ronjon Chakraverty1, Premini Mahendra2, Charles Craddock1,2, and Paul A.H. Moss1,2

1 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, England, UK
2 Department of Haematology, Queen Elizabeth Hospital, Birmingham B15 2TH, England, UK
3 Department of Virology, Queen Elizabeth Hospital, Birmingham B15 2TH, England, UK
4 National Blood Transfusion Service, Birmingham B15 2SG, England, UK
5 Miltenyi Biotec GmbH, Bergisch Gladbach 51429, Germany
6 Department of Haematology, Royal Hospital for Children, Bristol BS2 8BJ, England, UK
7 Department of Haematology, Hammersmith Hospital, Imperial College, London W12 0HS, England, UK

CORRESPONDENCE Paul A.H. Moss: p.moss{at}bham.ac.uk

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA–peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 x 103/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.


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