Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation

被引:117
|
作者
Micklethwaite, Kenneth
Hansen, Anna
Foster, Aaron
Snape, Elizabeth
Antonenas, Vicki
Sartar, Mary
Shaw, Peter
Bradstock, Ken
Gottlieb, David
机构
[1] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Sydney, NSW 2006, Australia
[2] Westmead Hosp, Sydney Cellular Therapies Lab, Westmead, NSW 2145, Australia
[3] Westmead Hosp, Blood & Marrow Transplant Serv, Westmead, NSW 2145, Australia
[4] Childrens Hosp Westmead, Sydney, NSW, Australia
关键词
cytomegalovirus; immunotherapy; hematopoietic stem cell transplant;
D O I
10.1016/j.bbmt.2007.02.004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2007 American Society for Blood and Marrow Transplantation.
引用
收藏
页码:707 / 714
页数:8
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