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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2003-01-0297. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0297v1 102/2/497    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 Cavalieri, S. Articles by Bonini, C. Search for Related Content PubMed PubMed Citation Articles by Cavalieri, S. Articles by Bonini, C. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 497-505 GENE THERAPY Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence Simona Cavalieri, Sabrina Cazzaniga, Massimo Geuna, Zulma Magnani, Claudio Bordignon, Luigi Naldini, and Chiara Bonini From the Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo Torino; and Cancer Immunotherapy and Gene Therapy Program, H. S. Raffaele, Milan, Italy. Gene transfer into T lymphocytes is currently being tested for the treatment of lymphohematologic disorders. We previously showed that suicide gene transfer into donor lymphocytes infused to treat leukemic relapse after allogeneic hematopoietic stem cell transplantation allowed control of graft-versus-host disease. However, the T-cell receptor (TCR) activation and sustained proliferation required for retroviral vector transduction may impair the half-life and immune competence of transduced cells and reduce graft-versus-leukemia activity. Thus, we tested lentiviral vectors (LVs) and stimulation with cytokines involved in antigen-independent T-cell homeostasis, such as interleukin 7 (IL-7), IL-2, and IL-15. Late-generation LVs transduced efficiently nonproliferating T cells that had progressed from G0 to the G1 phase of the cell cycle on cytokine treatment. Importantly, IL-2 and IL-7, but not IL-15, stimulation preserved physiologic CD4/CD8 and naive-memory ratios in transduced cells with only minor induction of some activation markers. Functional analysis of immune response to cytomegalovirus (CMV) showed that, although CMV-specific T cells were preserved by all conditions of transduction, proliferation and specific killing of autologous cells presenting a CMV epitope were higher for IL-2 and IL-7 than for IL-15. Thus, LV transduction of IL-2 or IL-7 prestimulated cells overcomes the limitations of retroviral vectors and may significantly improve the efficacy of T-cell–based gene therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kaneko, S. Mastaglio, A. Bondanza, M. Ponzoni, F. Sanvito, L. Aldrighetti, M. Radrizzani, S. La Seta-Catamancio, E. Provasi, A. Mondino, et al. IL-7 and IL-15 allow the generation of suicide gene-modified alloreactive self-renewing central memory human T lymphocytes Blood, January 29, 2009; 113(5): 1006 - 1015. [Abstract] [Full Text] [PDF] C. Frecha, C. Costa, D. Negre, E. Gauthier, S. J. 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