Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).
We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-gamma enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity.
Savoldo
Barbara
B
Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, 6621 Fannin St, MC 3-3320, Houston, TX 77030, USA. bsavoldo@bcm.tmc.edu
Goss
John A
JA
Hammer
Markus M
MM
Zhang
Lan
L
Lopez
Teresita
T
Gee
Adrian P
AP
Lin
Yu-Feng
YF
Quiros-Tejeira
Ruben E
RE
Reinke
Petra
P
Schubert
Stephan
S
Gottschalk
Stephen
S
Finegold
Milton J
MJ
Brenner
Malcolm K
MK
Rooney
Cliona M
CM
Heslop
Helen E
HE
D000956:Antigens, Viral / Q000097:blood; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007223:Infant; D017710:Lymphocyte Transfusion; D008297:Male; D012189:Retrospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*; D014181:Transplantation Immunology; D014182:Transplantation, Autologous
D000956:Antigens, Viral