title: Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).
abstract: 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.
authors.affiliation: 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
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.forename: John A
authors.initials: JA
authors.lastname: Goss
authors.forename: Markus M
authors.initials: MM
authors.lastname: Hammer
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Teresita
authors.initials: T
authors.lastname: Lopez
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Ruben E
authors.initials: RE
authors.lastname: Quiros-Tejeira
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Stephan
authors.initials: S
authors.lastname: Schubert
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
authors.forename: Milton J
authors.initials: MJ
authors.lastname: Finegold
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
mesh_terms: 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
chemical_list: D000956:Antigens, Viral