Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers.
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.
Cobbold
Mark
M
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, England, UK.
Khan
Naeem
N
Pourgheysari
Batoul
B
Tauro
Sudhir
S
McDonald
Dorothy
D
Osman
Husam
H
Assenmacher
Mario
M
Billingham
Lucinda
L
Steward
Colin
C
Crawley
Charles
C
Olavarria
Eduardo
E
Goldman
John
J
Chakraverty
Ronjon
R
Mahendra
Premini
P
Craddock
Charles
C
Moss
Paul A H
PA
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
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010455:Peptides