title: Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers.
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 x 10(3)/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.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Cobbold
authors.forename: Naeem
authors.initials: N
authors.lastname: Khan
authors.forename: Batoul
authors.initials: B
authors.lastname: Pourgheysari
authors.forename: Sudhir
authors.initials: S
authors.lastname: Tauro
authors.forename: Dorothy
authors.initials: D
authors.lastname: McDonald
authors.forename: Husam
authors.initials: H
authors.lastname: Osman
authors.forename: Mario
authors.initials: M
authors.lastname: Assenmacher
authors.forename: Lucinda
authors.initials: L
authors.lastname: Billingham
authors.forename: Colin
authors.initials: C
authors.lastname: Steward
authors.forename: Charles
authors.initials: C
authors.lastname: Crawley
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
authors.forename: John
authors.initials: J
authors.lastname: Goldman
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: Premini
authors.initials: P
authors.lastname: Mahendra
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Paul A H
authors.initials: PA
authors.lastname: Moss
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000628:therapy*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006402:Hematologic Diseases / Q000628:therapy / Q000821:virology; D006801:Humans; D008297:Male; D010455:Peptides / Q000276:immunology; D033581:Stem Cell Transplantation
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010455:Peptides