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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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Leen, A. M. Articles by Bollard, C. M. Search for Related Content PubMed PubMed Citation Articles by Leen, A. M. Articles by Bollard, C. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2009 Accepted August 10, 2009 Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplant Ann M. Leen*, Anne Christin, Gary D. Myers, Hao Liu, Conrad R. Cruz, Patrick J. Hanley, Alana A. Kennedy-Nasser, Kathryn S. Leung, Adrian P. Gee, Robert A. Krance, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, and Catherine M. Bollard Center for Cell and Gene Therapy, Baylor College of Medicine,Texas Children's Hospital and The Methodist Hospital, Houston, TX, United States * Corresponding author; email: amleen{at}txccc.org. 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 (CTLs) lines (5x106-1.35x108 cells/m2) with specificity for two commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplant recipients receiving partially HLA-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 >12 weeks, but the adenoviral-specific component only expanded in vivo in the presence of concomitant adenoviral infection and antigen. Nevertheless, adenovirus-specific T cells could still 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. Following infusion, none of these 13 high-risk recipients developed EBV-associated lymphoproliferative disease, while two of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenoviral-specific T cells can safely reconstitute an antigen responsive "memory" population of CTLs after HLA antigen-mismatched stem cell transplant, and may provide anti-viral activity. The trial described herein has been registered at www.ClinicalTrials.gov under identifier NCT00590083. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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