Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation.
Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation.
Micklethwaite
Kenneth
K
Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, Australia.
Hansen
Anna
A
Foster
Aaron
A
Snape
Elizabeth
E
Antonenas
Vicki
V
Sartor
Mary
M
Shaw
Peter
P
Bradstock
Ken
K
Gottlieb
David
D
D000293:Adolescent; D019264:Adoptive Transfer / Q000009:adverse effects / Q000379:methods*; D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000627:therapeutic use; D014775:Virus Activation
D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa