Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs)

Barbara Savoldo, John A. Goss, Markus M. Hammer, Lan Zhang, Teresita Lopez, Adrian P. Gee, Yu Feng Lin, Ruben E. Quiros-Tejeira, Petra Reinke, Stephan Schubert, Stephen Gottschalk, Milton J. Finegold, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop

Research output: Contribution to journalArticle

187 Citations (Scopus)

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-γ 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.

Original languageEnglish (US)
Pages (from-to)2942-2949
Number of pages8
JournalBlood
Volume108
Issue number9
DOIs
StatePublished - Nov 1 2006

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Transplants
T-cells
Cytotoxic T-Lymphocytes
Human Herpesvirus 4
Viruses
Therapeutics
Transplant Recipients
Enzyme-Linked Immunospot Assay
Eye Diseases
DNA
Lymphocytes
Polymerase chain reaction
Immunosuppression
Interferons
Antiviral Agents
Real-Time Polymerase Chain Reaction
Liver
Blood Cells
Toxicity
Assays

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Savoldo, B., Goss, J. A., Hammer, M. M., Zhang, L., Lopez, T., Gee, A. P., ... Heslop, H. E. (2006). Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). Blood, 108(9), 2942-2949. https://doi.org/10.1182/blood-2006-05-021782

Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). / Savoldo, Barbara; Goss, John A.; Hammer, Markus M.; Zhang, Lan; Lopez, Teresita; Gee, Adrian P.; Lin, Yu Feng; Quiros-Tejeira, Ruben E.; Reinke, Petra; Schubert, Stephan; Gottschalk, Stephen; Finegold, Milton J.; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.

In: Blood, Vol. 108, No. 9, 01.11.2006, p. 2942-2949.

Research output: Contribution to journalArticle

Savoldo, B, Goss, JA, Hammer, MM, Zhang, L, Lopez, T, Gee, AP, Lin, YF, Quiros-Tejeira, RE, Reinke, P, Schubert, S, Gottschalk, S, Finegold, MJ, Brenner, MK, Rooney, CM & Heslop, HE 2006, 'Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs)', Blood, vol. 108, no. 9, pp. 2942-2949. https://doi.org/10.1182/blood-2006-05-021782
Savoldo, Barbara ; Goss, John A. ; Hammer, Markus M. ; Zhang, Lan ; Lopez, Teresita ; Gee, Adrian P. ; Lin, Yu Feng ; Quiros-Tejeira, Ruben E. ; Reinke, Petra ; Schubert, Stephan ; Gottschalk, Stephen ; Finegold, Milton J. ; Brenner, Malcolm K. ; Rooney, Cliona M. ; Heslop, Helen E. / Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). In: Blood. 2006 ; Vol. 108, No. 9. pp. 2942-2949.
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