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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-08-2351. This Article Full Text (PDF) All Versions of this Article: 2002-08-2351v1 101/4/1290    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marktel, S. Articles by Bonini, C. Search for Related Content PubMed PubMed Citation Articles by Marktel, S. Articles by Bonini, C. Social Bookmarking                   What's this? Submitted August 13, 2002 Accepted September 24, 2002 Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T cell-depleted stem cell transplantation Sarah Marktel, Zulma Magnani, Fabio Ciceri, Sabrina Cazzaniga, Stanley R Riddell, Catia Traversari, Claudio Bordignon, and Chiara Bonini* Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H.S. Raffaele, Milan, Italy; Bone Marrow Transplantation Unit, Istituto Scientifico H.S. Raffaele, Milan, Italy Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H.S. Raffaele, Milan, Italy Bone Marrow Transplantation Unit, Istituto Scientifico H.S. Raffaele, Milan, Italy; Cancer Immunotherapy and Gene Therapy Program, Istituto Scientifico H.S. Raffaele, Milan, Italy Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, USA Molmed S.p.A., Milan, Italy * Corresponding author; email: chiara.bonini{at}hsr.it. We have previously shown that the infusion of donor lymphocytes expressing the HSV thymidine kinase (HSV-tk) gene is an efficient tool for controlling graft-versus-host disease (GvHD), while preserving graft-versus-leukemia (GvL). In addition to the GvL effect, administration of donor HSV-tk+ cells could have a clinical impact in promoting immune reconstitution after T cell depleted stem cell transplantation (SCT). To explore this hypothesis, we have investigated whether in vitro polyclonal activation, retroviral transduction, immunoselection and expansion affect the immune competence of donor T cells. We have observed that, after appropriate in vitro manipulation, T cells specific for antigens relevant in the context of SCT are preserved in terms of frequency, expression of T cell receptor, proliferation, cytokine secretion and lytic activity. A reduction in the frequency of allo-specific T cell precursors was observed after prolonged T cell culture, suggesting that cell manipulation protocols involving a short culture time and high transduction efficiency are needed. Finally, the long term persistence of HSV-tk+ cells was observed in a patient treated in the GvL clinical trial, and a reversion of the phenotype of HSV-tk+ cells from CD45RO+ to CD45RA+ was documented more than 2 years after the infusion. Based on all these evidences, we propose a clinical study of preemptive infusions of donor HSV-tk+ T cells after SCT from haplo-identical donors, to provide early immune reconstitution against infections and potential immune protection against disease recurrence. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Ciceri, C. Bonini, S. Marktel, E. Zappone, P. Servida, M. Bernardi, A. Pescarollo, A. Bondanza, J. Peccatori, S. Rossini, et al. Antitumor effects of HSV-TK engineered donor lymphocytes after allogeneic stem-cell transplantation Blood, June 1, 2007; 109(11): 4698 - 4707. [Abstract] [Full Text] [PDF] C. Berger, M. E. Flowers, E. H. Warren, and S. R. Riddell Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation Blood, March 15, 2006; 107(6): 2294 - 2302. [Abstract] [Full Text] [PDF] A. Bondanza, V. Valtolina, Z. Magnani, M. Ponzoni, K. Fleischhauer, M. Bonyhadi, C. Traversari, F. Sanvito, S. Toma, M. Radrizzani, et al. Suicide gene therapy of graft-versus-host disease induced by central memory human T lymphocytes Blood, March 1, 2006; 107(5): 1828 - 1836. [Abstract] [Full Text] [PDF] A. Recchia, C. Bonini, Z. Magnani, F. Urbinati, D. Sartori, S. Muraro, E. Tagliafico, A. Bondanza, M. T. L. Stanghellini, M. Bernardi, et al. Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells PNAS, January 31, 2006; 103(5): 1457 - 1462. [Abstract] [Full Text] [PDF] C. Imai, S. Iwamoto, and D. Campana Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells Blood, July 1, 2005; 106(1): 376 - 383. [Abstract] [Full Text] [PDF] J. Bae, J. A. Martinson, and H. G. Klingemann Identification of CD19 and CD20 Peptides for Induction of Antigen-Specific CTLs against B-Cell Malignancies Clin. Cancer Res., February 15, 2005; 11(4): 1629 - 1638. [Abstract] [Full Text] [PDF] H. E. Heslop, F. K. Stevenson, and J. J. Molldrem Immunotherapy of Hematologic Malignancy Hematology, January 1, 2003; 2003(1): 331 - 349. [Abstract] [Full Text] [PDF]

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