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

Mark Cobbold, Naeem Khan, Batoul Pourgheysari, Sudhir Tauro, Dorothy McDonald, Husam Osman, Mario Assenmacher, Lucinda Billingham, Colin Steward, Charles Crawley, Eduardo Olavarria, John Goldman, Ronjon Chakraverty, Premini Mahendra, Charles Craddock, Paul A. H. Moss

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    Abstract

    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 × 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.
    Original languageEnglish
    Pages (from-to)379-386
    Number of pages8
    JournalJournal of Experimental Medicine
    Volume202
    Issue number3
    DOIs
    Publication statusPublished - 2005

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  • Cite this

    Cobbold, M., Khan, N., Pourgheysari, B., Tauro, S., McDonald, D., Osman, H., Assenmacher, M., Billingham, L., Steward, C., Crawley, C., Olavarria, E., Goldman, J., Chakraverty, R., Mahendra, P., Craddock, C., & Moss, P. A. H. (2005). Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers. Journal of Experimental Medicine, 202(3), 379-386. https://doi.org/10.1084/jem.20040613