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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1828-1836. Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-09-3716. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3716v1 107/5/1828    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 Bondanza, A. Articles by Bonini, C. Search for Related Content PubMed PubMed Citation Articles by Bondanza, A. Articles by Bonini, C. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Suicide gene therapy of graft-versus-host disease induced by central memory human T lymphocytes Attilio Bondanza, Veronica Valtolina, Zulma Magnani, Maurilio Ponzoni, Katharina Fleischhauer, Mark Bonyhadi, Catia Traversari, Francesca Sanvito, Salvatore Toma, Marina Radrizzani, Simona La Seta-Catamancio, Fabio Ciceri, Claudio Bordignon, and Chiara Bonini From the Experimental Hematology Laboratory, Cancer Immunotherapy and Gene Therapy Program, Università Vita-Salute S. Raffaele, Pathology Unit, Telethon Institute for Gene Therapy, S. Raffaele Scientific Institute, Milan, Italy; Xcyte Therapies, Seattle, WA; and Molmed SpA, Milan, Italy. In allogeneic hematopoietic cell transplantation (allo-HCT), the immune recognition of host antigens by donor T lymphocytes leads to a beneficial graft-versus-leukemia (GvL) effect as well as to life-threatening graft-versus-host disease (GvHD). Genetic modification of T lymphocytes with a retroviral vector (RV) expressing the herpes simplex virus-thymidine kinase (TK) suicide gene confers selective sensitivity to the prodrug ganciclovir (GCV). In patients, the infusion of TK+ lymphocytes and the subsequent administration of GCV resulted in a time-wise modulation of antihost reactivity for a GvL effect, while controlling GvHD. Because activation required for genetic modification with RV may reduce antihost reactivity, we investigated the requirements for maximizing the potency of human TK+ lymphocytes. Whereas T-cell receptor triggering alone led to effector memory (EM) TK+ lymphocytes, the addition of CD28 costimulation through cell-sized beads resulted in the generation of central memory (CM) TK+ lymphocytes. In a quantitative model for GvHD using nonobese diabetic/severely combined immunodeficient mice, CM TK+ lymphocytes were more potent than EM TK+ lymphocytes. GCV administration efficiently controlled GvHD induced by CM TK+ lymphocytes. These results warrant the clinical investigation of CM suicide gene-modified human T lymphocytes for safe and effective allo-HCT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. J. Barrett Leukemia Vaccines to Boost the Graft-versus-Leukemia Effect after Allogeneic Stem Cell Transplantation ASCO Educational Book, January 1, 2008; 2008(1): 330 - 333. [Abstract] [Full Text] [PDF] M. Deschamps, P. Mercier-Lethondal, J. M. Certoux, C. Henry, B. Lioure, C. Pagneux, J. Y. Cahn, E. Deconinck, E. Robinet, P. Tiberghien, et al. Deletions within the HSV-tk transgene in long-lasting circulating gene-modified T cells infused with a hematopoietic graft Blood, December 1, 2007; 110(12): 3842 - 3852. [Abstract] [Full Text] [PDF]

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