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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1958-1967. Prepublished online as a Blood First Edition Paper on May 14, 2009; DOI 10.1182/blood-2009-03-213256. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-03-213256v1 114/9/1958    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 Google Scholar Articles by Hanley, P. J. Articles by Bollard, C. M. PubMed PubMed Citation Articles by Hanley, P. J. Articles by Bollard, C. M. Related Collections Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes Patrick J. Hanley1,2, Conrad Russell Young Cruz1, Barbara Savoldo1,3, Ann M. Leen1,3, Maja Stanojevic1, Mariam Khalil1, William Decker4, Jeffrey J. Molldrem4, Hao Liu1,5, Adrian P. Gee1,3, Cliona M. Rooney1,3,6, Helen E. Heslop13, Gianpietro Dotti1,2,5, Malcolm K. Brenner13, Elizabeth J. Shpall4, and Catherine M. Bollard13,5 1 Center for Cell and Gene Therapy and Departments of 2 Immunology and 3 Pediatrics, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston; 4 Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M. D. Anderson Cancer Center, Houston; and Departments of 5 Medicine and 6 Virology, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston The naive phenotype of cord blood (CB) T cells may reduce graft-versus-host disease after umbilical cord blood transplantation, but this naivety and their low absolute numbers also delays immune reconstitution, producing higher infection-related mortality that is predominantly related to CMV, adenovirus (Adv), and EBV. Adoptive immunotherapy with peripheral blood-derived virus-specific cytotoxic T lymphocytes (CTLs) can effectively prevent viral disease after conventional stem cell transplantation, and we now describe the generation of single cultures of CTLs from CB that are specific for multiple viruses. Using EBV-infected B cells transduced with a clinical-grade Ad5f35CMVpp65 adenoviral vector as sources of EBV, Adv, and CMV antigens, we expanded virus-specific T cells even from CB T cells with a naive phenotype. After expansion, each CTL culture contained both CD8+ and CD4+ T-cell subsets, predominantly of effector memory phenotype. Each CTL culture also had HLA-restricted virus-specific cytotoxic effector function against EBV, CMV, and Adv targets. The CB CTLs recognized multiple viral epitopes, including CD4-restricted Adv-hexon epitopes and immunosubdominant CD4- and CD8-restricted CMVpp65 epitopes. Notwithstanding their naive phenotype, it is therefore possible to generate trivirus-specific CTLs in a single culture of CB, which may be of value to prevent or treat viral disease in CB transplant recipients. This study is registered at www.clinicaltrials.gov as NCT00078533 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Expanding multiviral reactive T cells from cord blood Richard W. Childs and Christa S. Zerbe Blood 2009 114: 1725-1726. [Abstract] [Full Text] [PDF] This article has been cited by other articles: C. S. Hinrichs, Z. A. Borman, L. Cassard, L. Gattinoni, R. Spolski, Z. Yu, L. Sanchez-Perez, P. Muranski, S. J. Kern, C. Logun, et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity PNAS, October 13, 2009; 106(41): 17469 - 17474. [Abstract] [Full Text] [PDF] R. W. Childs and C. S. Zerbe Expanding multiviral reactive T cells from cord blood Blood, August 27, 2009; 114(9): 1725 - 1726. [Abstract] [Full Text] [PDF]

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