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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4283-4292. Prepublished online as a Blood First Edition Paper on August 21, 2009; DOI 10.1182/blood-2009-07-232454. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-07-232454v1 114/19/4283    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 CrossRef Google Scholar Articles by Leen, A. M. Articles by Bollard, C. M. PubMed PubMed Citation Articles by Leen, A. M. Articles by Bollard, C. M. Related Collections Immunobiology Transplantation Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION 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 Ann M. Leen1, Anne Christin1, Gary D. Myers1, Hao Liu1, Conrad R. Cruz1, Patrick J. Hanley1, Alana A. Kennedy-Nasser1, Kathryn S. Leung1, Adrian P. Gee1, Robert A. Krance1, Malcolm K. Brenner1, Helen E. Heslop1, Cliona M. Rooney1, and Catherine M. Bollard1 1 Center for Cell and Gene Therapy and Departments of Pediatrics, Immunology, Medicine, and Virology, Baylor College of Medicine, Texas Children's Hospital and the Methodist Hospital, Houston Viral infection or reactivation remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. We now show that infusions of single cytotoxic T lymphocyte (CTL) lines (5 x 106-1.35 x 108 cells/m2) with specificity for 2 commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplantation recipients receiving partially human leukocyte antigen–matched and haploidentical stem cell grafts (n = 13), without inducing graft-versus-host disease. The EBV-specific component of the CTLs expanded in vivo and persisted for more than 12 weeks, but the adenovirus-specific component only expanded in vivo in the presence of concomitant adenoviral infection. Nevertheless, adenovirus-specific T cells could be detected for at least 8 weeks in peripheral blood, even in CTL recipients without viral infection, provided the adenovirus-specific component of their circulating lymphocytes was first expanded by exposure to adenoviral antigens ex vivo. After infusion, none of these 13 high-risk recipients developed EBV-associated lymphoproliferative disease, while 2 of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenovirus-specific T cells can safely reconstitute an antigen responsive "memory" population of CTLs after human leukocyte antigen–mismatched stem cell transplantation and may provide antiviral activity. This trial was registered at www.clinicaltrials.gov as #NCT00590083 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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