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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-01-0039. This Article Full Text (PDF) All Versions of this Article: 2002-01-0039v1 100/12/4059    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Savoldo, B. Articles by Rooney, C. M Search for Related Content PubMed PubMed Citation Articles by Savoldo, B. Articles by Rooney, C. M Social Bookmarking                   What's this? Submitted January 16, 2002 Accepted May 25, 2002 Autologous Epstein-Barr Virus (EBV)-Specific Cytotoxic T Cells for the treatment of Persistent Active EBV Infection Barbara Savoldo, M Helen Huls, Zhensheng Liu, Takayuki Okamura, Hans-Dieter Volk, Petra Reinke, Robert Sabat, Nina Babel, James F Jones, Jennifer Webster-Cyriaque, Adrian P Gee, Malcolm K Brenner, Helen E Heslop, and Cliona M Rooney* Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA Department of Medical Immunology, Charite Hospital, University of Berlin, Berlin, Germany Department of Nephrology, Charite Hospital, University of Berlin, Berlin, Germany Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA * Corresponding author; email: crooney{at}bcm.tmc.edu. Chronic Active Epstein-Barr Virus-infection (CAEBV) syndrome is a heterogeneous EBV-related disorder characterized by chronic fatigue, fever, lymphadenopathy and/or hepato-splenomegaly, associated with abnormal patterns of antibody to EBV. CAEBV can range from disabling mild/moderate forms to rapidly lethal disorders. Even patients with mild/moderate disease frequently suffer adverse effects from long-term anti-inflammatory agents and have a quality of life that progressively deteriorates. It is still unknown why these individuals are unable to produce an effective immune-response to control EBV and no effective treatment is currently available. Since ex-vivo expanded EBV-specific cytotoxic T-lymphocytes (EBV-CTL) can safely restore EBV-specific cellular immune-responses in immunodeficient patients, we assessed the possibility that adoptive immunotherapy might also effectively treat CAEBV-infection. Following stimulation with irradiated EBV-transformed lymphoblastoid cell lines (LCL), EBV-CTL were successfully generated from 8/8 patients with the mild/moderate form of CAEBV-infection. These CTL were predominantly CD3+CD8+ cells and produced specific killing of the autologous LCL. Five of these patients, with 1 to 12-year histories of disease were treated with 1 to 4 injections of EBV-CTL. Following infusion, there was resolution of fatigue and malaise, disappearance of fever and regression of lymphadenopathy and splenomegaly. The pattern and titers of anti-EBV antibodies also normalized. No toxicity was observed. Four patients did not show any relapse of disease within 6-36 months follow-up; one patient had recurrence of fatigue and myalgia 1 year post-CTL infusion. We suggest that adoptive immunotherapy with autologous EBV-CTL may represent a safe and feasible alternative treatment for patients affected with mild/moderate CAEBV-infection and that this approach should be evaluated in the more severe forms of the disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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., September 1, 2009; 20(9): 1472 - 1482. [Abstract] [Full Text] [PDF] C. Quintarelli, G. Dotti, B. De Angelis, V. Hoyos, M. Mims, L. Luciano, H. E. Heslop, C. M. Rooney, F. Pane, and B. Savoldo Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia Blood, September 1, 2008; 112(5): 1876 - 1885. 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