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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.
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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.
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