|
|
Blood, 1 November 2006, Vol. 108, No. 9, pp. 2942-2949.
Prepublished online as a Blood First Edition Paper on July 11, 2006; DOI 10.1182/blood-2006-05-021782.
 Previous Article | Table of Contents | Next Article 
CLINICAL TRIALS AND OBSERVATIONS
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, and
Helen E. Heslop
From the Center for Cell and Gene Therapy, Departments of Pediatrics, Surgery, Pathology, Medicine, and Molecular Virology and Microbiology, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, TX; Department of Nephrology and Internal Intensive Care, Charité–Universitätsmedizin Berlin, Berlin, Germany; and German Heart Center Berlin, Berlin, Germany.
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- 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Hiding in plain sight
- Richard F. Ambinder
Blood 2006 108: 2891.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
J. I. Cohen, H. Kimura, S. Nakamura, Y.-H. Ko, and E. S. Jaffe
Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008
Ann. Onc.,
June 10, 2009;
(2009)
mdp064v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. McAulay, T. Haque, G. Urquhart, C. Bellamy, D. Guiretti, and D. H. Crawford
Epitope Specificity and Clonality of EBV-Specific CTLs Used to Treat Posttransplant Lymphoproliferative Disease
J. Immunol.,
March 15, 2009;
182(6):
3892 - 3901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Dudley and S. A. Rosenberg
Clinical Trials Investigating Adoptive Cell Therapy Combined with Lymphodepletion for Patients with Advanced Cancer
ASCO Educational Book,
January 1, 2009;
2009(1):
516 - 520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Gulley and W. Tang
Laboratory Assays for Epstein-Barr Virus-Related Disease
J. Mol. Diagn.,
July 1, 2008;
10(4):
279 - 292.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Carbone, A. Gloghini, and G. Dotti
EBV-Associated Lymphoproliferative Disorders: Classification and Treatment
Oncologist,
May 1, 2008;
13(5):
577 - 585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Elliott, A. Suhrbier, J. J. Miles, G. Lawrence, S. J. Pye, T. T. Le, A. Rosenstengel, T. Nguyen, A. Allworth, S. R. Burrows, et al.
Phase I Trial of a CD8+ T-Cell Peptide Epitope-Based Vaccine for Infectious Mononucleosis
J. Virol.,
February 1, 2008;
82(3):
1448 - 1457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bhaduri-McIntosh, M. J. Rotenberg, B. Gardner, M. Robert, and G. Miller
Repertoire and frequency of immune cells reactive to Epstein-Barr virus-derived autologous lymphoblastoid cell lines
Blood,
February 1, 2008;
111(3):
1334 - 1343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Bakker and G. W. van Imhoff
Post-transplant lymphoproliferative disorders: from treatment to early detection and prevention?
Haematologica,
November 1, 2007;
92(11):
1447 - 1450.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Quintarelli, J. F. Vera, B. Savoldo, G. M. P. Giordano Attianese, M. Pule, A. E. Foster, H. E. Heslop, C. M. Rooney, M. K. Brenner, and G. Dotti
Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes
Blood,
October 15, 2007;
110(8):
2793 - 2802.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Savoldo, C. M. Rooney, A. Di Stasi, H. Abken, A. Hombach, A. E. Foster, L. Zhang, H. E. Heslop, M. K. Brenner, and G. Dotti
Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30{zeta} artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease
Blood,
October 1, 2007;
110(7):
2620 - 2630.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Haque, G. M. Wilkie, M. M. Jones, C. D. Higgins, G. Urquhart, P. Wingate, D. Burns, K. McAulay, M. Turner, C. Bellamy, et al.
Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial
Blood,
August 15, 2007;
110(4):
1123 - 1131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
