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Blood First Edition Paper, prepublished online January 28, 2010; DOI 10.1182/blood-2009-09-242263. This Article Full Text (PDF) Supplemental Figures 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 Google Scholar Articles by Micklethwaite, K. P. Articles by Dotti, G. PubMed PubMed Citation Articles by Micklethwaite, K. P. Articles by Dotti, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 9, 2009; accepted January 8, 2010. Derivation of human T-lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation Kenneth P. Micklethwaite1, Barbara Savoldo2, Patrick J. Hanley3, Ann M. Leen1, Gail J. Demmler-Harrison4, Laurence J.N. Cooper5, Hao Liu6, Adrian P. Gee1, Elizabeth J. Shpall5, Cliona M. Rooney1, Helen E. Heslop1, Malcolm K. Brenner1, Catherine M. Bollard1 and Gianpietro Dotti1,* 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston, Texas; 2 Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston, Texas; 3 Department of Immunology, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston, Texas; 4 Department of Pathology, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston, Texas; 5 Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, Texas; 6 Department of Medicine, Baylor College of Medicine, Texas Children's Hospital and The Methodist Hospital, Houston, Texas * Corresponding author; email: gdotti{at}bcm.tmc.edu Abstract Viral infections and leukemic relapse account for the majority of treatment failures in patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving allogeneic hematopoietic stem cell (HSC) or cord blood (CB) transplants. Adoptive transfer of virus-specific cytotoxic T-lymphocytes (CTLs) provides protection against common viruses causing serious infections after HSC transplants without concomitant graft-versus-host-disease. We have now generated CTL lines from peripheral blood (PB) or CB units that recognize multiple common viruses and provide antileukemic activity by transgenic expression of a chimeric antigen receptor (CAR) targeting CD19 expressed on B-ALL. PB-derived CAR+ CTLs produced IFN in response to cytomegalovirus-pp65, adenovirus-hexon and Epstein-Barr virus pepmixes (from, 205±104 to 1034±304 SFC/105 T-cells) and lysed primary B-ALL blasts in Cr release assays (mean 66%±5% specific lysis, E:T ratio 40:1) and the CD19+ Raji cell line (mean 78%±17%) in contrast to non-transduced controls (8%±8% and 3%±2%). CB-derived CAR+ CTLs showed similar antiviral and antitumor function and both PB and CB CAR+ CTL completely eliminated B-ALL blasts over 5 days coculture. This approach may prove beneficial for patients with high-risk B-ALL who have recently received an HSC or CB transplant and are at risk of infection and relapse. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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