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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2442-2450. Prepublished online as a Blood First Edition Paper on October 29, 2008; DOI 10.1182/blood-2008-05-157222. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-05-157222v1 113/11/2442    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Louis, C. U. Articles by Gottschalk, S. Search for Related Content PubMed PubMed Citation Articles by Louis, C. U. Articles by Gottschalk, S. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients Chrystal U. Louis13, Karin Straathof13, Catherine M. Bollard14, Claudia Gerken13, M. Helen Huls13, M. Victoria Gresik4,5, Meng-Fen Wu4, Heidi L. Weiss4, Adrian P. Gee14, Malcolm K. Brenner14,6,7, Cliona M. Rooney14,8,9, Helen E. Heslop14,6, and Stephen Gottschalk14,8 1 Center for Cell and Gene Therapy, 2 Texas Children's Cancer Center, 3 Department of Pediatrics, 4 The Dan L. Duncan Cancer Center, and the Departments of 5 Pathology, 6 Medicine, 7 Molecular and Human Genetics, 8 Immunology, and 9 Molecular Virology and Microbiology, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital, Houston, TX Treatment of Epstein-Barr virus (EBV)–positive nasopharyngeal carcinoma (NPC) with EBV-specific cytotoxic T cells (EBV-specific CTL) has been promising, producing clinical responses. However, infused EBV-specific CTL did not expand in vivo, likely limiting their antitumor activity. Lymphodepleting patients with chemotherapy before T-cell transfer enhances in vivo T-cell expansion, but results in nonspecific destruction of the resident immune system and can have significant toxicity. To evaluate if monoclonal antibodies (mAbs) can produce a more selective lymphodepletion, we conducted a clinical study in which NPC patients received a pair of lymphodepleting mAbs targeted to the CD45 antigen (CD45 mAbs) before EBV-specific CTL infusion. Eight patients with recurrent NPC received CD45 mAbs followed by escalating doses of auto-logous EBV-specific CTL. Infusion of CD45 mAbs resulted in transient lymphopenia in all patients and an increase in interleukin-15 (IL-15) levels in 6 out 8 patients. All patients had an increase in their peripheral blood frequency of EBV-specific T cells after CTL infusion. Three patients with a persistent increase had clinical benefits including 1 complete response (> 24 months) and 2 with stable disease (for 12 and 15 months). Lymphodepleting mAbs prior CTL transfer may represent an alternative to chemotherapy to enhance expansion of infused CTL. This study is registered at http://www.clinialtrials.gov as NCT00608257 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Leen, A. Christin, G. D. Myers, H. Liu, C. R. Cruz, P. J. Hanley, A. A. Kennedy-Nasser, K. S. Leung, A. P. Gee, R. A. Krance, et al. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation Blood, November 5, 2009; 114(19): 4283 - 4292. [Abstract] [Full Text] [PDF] 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]

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