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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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Submitted May 9, 2006
Accepted June 19, 2006

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

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

Center for Cell & Gene Therapy, Dept. of Pediatrics, Baylor College of Medicine, Houston, TX, USA
Dept. of Surgery, Baylor College of Medicine, The Methodist Hospital & Texas Children's Hospital, TX
Dept. of Nephrology & Intensive Care, Charite - Universitatsmedizin Berlin, Germany
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
German Heart Center Berlin, Germany
Dept. Pediatrics & Pathology, Baylor College of Medicine, Texas Childrens Hospital, Houston,TX, USA

* Corresponding author; email: bsavoldo{at}bcm.tmc.edu.

We have investigated the in-vivo safety, efficacy and persistence of autologous Epstein Barr Virus (EBV)-specific cytotoxic T lymphocytes (CTL) for the treatment solid organ transplant (SOT) recipients at high-risk for EBV-associated post-transplant lymphoproliferative disease (PTLD). EBV-CTL 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 (LCL). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time 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-g Elispot assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to pre-infusion levels after 2-6 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-CTL, that is limited in the presence of continued immunosuppression, but that nonetheless produces clinically useful anti-viral activity.


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