|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 April 2002, Vol. 99, No. 7, pp. 2592-2598
TRANSPLANTATION
Infusion of autologous Epstein-Barr virus (EBV)-specific
cytotoxic T cells for prevention of EBV-related lymphoproliferative
disorder in solid organ transplant recipients with evidence of active
virus replication
Patrizia Comoli,
Massimo Labirio,
Sabrina Basso,
Fausto Baldanti,
Paolo Grossi,
Milena Furione,
Mario Viganò,
Roberto Fiocchi,
Giorgio Rossi,
Fabrizio Ginevri,
Bruno Gridelli,
Antonia Moretta,
Daniela Montagna,
Franco Locatelli,
Giuseppe Gerna, and
Rita Maccario
From the Department of Pediatrics, Viral Diagnostic
Service, and Department of Heart Surgery, IRCCS Policlinico S. Matteo,
Pavia, Italy; the Department of Medicine and Public Health,
Università dell' Insubria, Varese, Italy; the Cardiovascular
Department and Liver Transplant Center, Ospedali Riuniti, Bergamo,
Italy; the Liver Transplant Center, Ospedale Maggiore, Milano, Italy;
and the Department of Pediatric Nephrology, Istituto G. Gaslini,
Genova, Italy.
Epstein-Barr virus (EBV)-associated posttransplantation
lymphoproliferative disorders (PTLDs) are a well-recognized
complication of immunosuppression in solid organ transplant recipients.
The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of
prophylactic/preemptive intervention are warranted to improve PTLD
outcome in this setting. We assessed whether transfer of EBV-specific
cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral
blood of allograft recipients receiving immunosuppression could
increase EBV-specific killing in vivo without augmenting the
probability of graft rejection. Autologous EBV-specific CTLs were
generated for 23 patients who were identified as being at risk of
developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL
transfer was well tolerated, and none of the patients showed any
evidence of rejection. An increase of the EBV-specific cytotoxicity was
observed after infusion, notwithstanding continuation of
immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease
in 5 patients, whereas in the other 2 graft recipients CTL transfer had
no apparent stable effect on EBV load. Our data suggest that the
infusion of autologous EBV-specific CTLs obtained from peripheral blood
mononuclear cells recovered at the time of viral reactivation is able
to augment virus-specific immune response and to reduce viral load in
organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in
these patients, following a strategy of preemptive therapy guided by
EBV DNA levels.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. Comoli
Arming CTLs against immunosuppressors
Blood,
November 26, 2009;
114(23):
4759 - 4760.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. De Angelis, G. Dotti, C. Quintarelli, L. E. Huye, L. Zhang, M. Zhang, F. Pane, H. E. Heslop, M. K. Brenner, C. M. Rooney, et al.
Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506)
Blood,
November 26, 2009;
114(23):
4784 - 4791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Brewin, C. Mancao, K. Straathof, H. Karlsson, S. Samarasinghe, P. J. Amrolia, and M. Pule
Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease
Blood,
November 26, 2009;
114(23):
4792 - 4803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Long, J. Zuo, A. M. Leese, N. H. Gudgeon, H. Jia, G. S. Taylor, and A. B. Rickinson
CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus-transformed B cells
Blood,
July 23, 2009;
114(4):
807 - 815.
[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]
|
|
|
|
|
|
|
F. Baldanti, M. Gatti, M. Furione, S. Paolucci, C. Tinelli, P. Comoli, P. Merli, and F. Locatelli
Kinetics of Epstein-Barr Virus DNA Load in Different Blood Compartments of Pediatric Recipients of T-Cell-Depleted HLA-Haploidentical Stem Cell Transplantation
J. Clin. Microbiol.,
November 1, 2008;
46(11):
3672 - 3677.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Y. Zafar, D. N. Howell, and J. P. Gockerman
Malignancy After Solid Organ Transplantation: An Overview
Oncologist,
July 1, 2008;
13(7):
769 - 778.
[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. 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]
|
|
|
|
|
|
|
A. P. Barry, G. Silvestri, J. T. Safrit, B. Sumpter, N. Kozyr, H. M. McClure, S. I. Staprans, and M. B. Feinberg
Depletion of CD8+ Cells in Sooty Mangabey Monkeys Naturally Infected with Simian Immunodeficiency Virus Reveals Limited Role for Immune Control of Virus Replication in a Natural Host Species
J. Immunol.,
June 15, 2007;
178(12):
8002 - 8012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Montagna, R. Maccario, F. Locatelli, E. Montini, S. Pagani, F. Bonetti, L. Daudt, I. Turin, D. Lisini, C. Garavaglia, et al.
Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia
Blood,
December 1, 2006;
108(12):
3843 - 3850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Savoldo, J. A. Goss, M. M. Hammer, L. Zhang, T. Lopez, A. P. Gee, Y.-F. Lin, R. E. Quiros-Tejeira, P. Reinke, S. Schubert, et al.
Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs)
Blood,
November 1, 2006;
108(9):
2942 - 2949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Willemsen, Z. Sebestyen, C. Ronteltap, C. Berrevoets, J. Drexhage, and R. Debets
CD8{alpha} Coreceptor to Improve TCR Gene Transfer to Treat Melanoma: Down-Regulation of Tumor-Specific Production of IL-4, IL-5, and IL-10
J. Immunol.,
July 15, 2006;
177(2):
991 - 998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Choquet, V. Leblond, R. Herbrecht, G. Socie, A.-M. Stoppa, P. Vandenberghe, A. Fischer, F. Morschhauser, G. Salles, W. Feremans, et al.
Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study
Blood,
April 15, 2006;
107(8):
3053 - 3057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Schaft, B. Lankiewicz, J. Drexhage, C. Berrevoets, D. J. Moss, V. Levitsky, M. Bonneville, S. P. Lee, A. J. McMichael, J.-W. Gratama, et al.
T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFN{gamma} production
Int. Immunol.,
April 1, 2006;
18(4):
591 - 601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Williams and D. H. Crawford
Epstein-Barr virus: the impact of scientific advances on clinical practice
Blood,
February 1, 2006;
107(3):
862 - 869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Comoli, P. Pedrazzoli, R. Maccario, S. Basso, O. Carminati, M. Labirio, R. Schiavo, S. Secondino, C. Frasson, C. Perotti, et al.
Cell Therapy of Stage IV Nasopharyngeal Carcinoma With Autologous Epstein-Barr Virus-Targeted Cytotoxic T Lymphocytes
J. Clin. Oncol.,
December 10, 2005;
23(35):
8942 - 8949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. M. Ghobrial, T. M. Habermann, M. J. Maurer, S. M. Geyer, K. M. Ristow, T. S. Larson, R. C. Walker, S. M. Ansell, W. R. Macon, G. G. Gores, et al.
Prognostic Analysis for Survival in Adult Solid Organ Transplant Recipients With Post-Transplantation Lymphoproliferative Disorders
J. Clin. Oncol.,
October 20, 2005;
23(30):
7574 - 7582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C. M. Straathof, C. M. Bollard, U. Popat, M. H. Huls, T. Lopez, M. C. Morriss, M. V. Gresik, A. P. Gee, H. V. Russell, M. K. Brenner, et al.
Treatment of nasopharyngeal carcinoma with Epstein-Barr virus-specific T lymphocytes
Blood,
March 1, 2005;
105(5):
1898 - 1904.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Heslop
Biology and Treatment of Epstein-Barr Virus-Associated Non-Hodgkin Lymphomas
Hematology,
January 1, 2005;
2005(1):
260 - 266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Bollard, L. Aguilar, K. C. Straathof, B. Gahn, M. H. Huls, A. Rousseau, J. Sixbey, M. V. Gresik, G. Carrum, M. Hudson, et al.
Cytotoxic T Lymphocyte Therapy for Epstein-Barr Virus+ Hodgkin's Disease
J. Exp. Med.,
December 20, 2004;
200(12):
1623 - 1633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Islas-Ohlmayer, A. Padgett-Thomas, R. Domiati-Saad, M. W. Melkus, P. D. Cravens, M. d. P. Martin, G. Netto, and J. V. Garcia
Experimental Infection of NOD/SCID Mice Reconstituted with Human CD34+ Cells with Epstein-Barr Virus
J. Virol.,
December 15, 2004;
78(24):
13891 - 13900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Comoli, R. De Palma, S. Siena, A. Nocera, S. Basso, F. Del Galdo, R. Schiavo, O. Carminati, A. Tagliamacco, G. F. Abbate, et al.
Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma
Ann. Onc.,
January 1, 2004;
15(1):
113 - 117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Comoli, S. Basso, A. Azzi, A. Moretta, R. De Santis, F. Del Galdo, R. De Palma, U. Valente, A. Nocera, F. Perfumo, et al.
Dendritic Cells Pulsed with Polyomavirus BK Antigen Induce Ex Vivo Polyoma BK Virus-Specific Cytotoxic T-Cell Lines in Seropositive Healthy Individuals and Renal Transplant Recipients
J. Am. Soc. Nephrol.,
December 1, 2003;
14(12):
3197 - 3204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. C.M. Straathof, C. M. Bollard, C. M. Rooney, and H. E. Heslop
Immunotherapy for Epstein-Barr Virus-Associated Cancers in Children
Oncologist,
February 1, 2003;
8(1):
83 - 98.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Heslop, F. K. Stevenson, and J. J. Molldrem
Immunotherapy of Hematologic Malignancy
Hematology,
January 1, 2003;
2003(1):
331 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
