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Blood, 15 January 2004, Vol. 103, No. 2, pp. 492-499. Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-07-2324. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2324v1 103/2/492    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 Morris, J. C. Articles by Kiem, H.-P. Search for Related Content PubMed PubMed Citation Articles by Morris, J. C. Articles by Kiem, H.-P. Related Collections Immunobiology Transplantation Oncogenes and Tumor Suppressors Gene Therapy Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Induction of cytotoxic T-lymphocyte responses to enhanced green and yellow fluorescent proteins after myeloablative conditioning Julia C. Morris, Melissa Conerly, Bobbie Thomasson, Jan Storek, Stanley R. Riddell, and Hans-Peter Kiem From the Clinical Research Division, Fred Hutchinson Cancer Research Center, and the Department of Medicine, University of Washington School of Medicine, Seattle. Lentiviral vectors are increasingly being used for transferring genes into hematopoietic stem cells (HSCs) due to their ability to transduce nondividing cells. Whereas results in in vitro studies and the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) model have been highly encourgaging, studies in large animals have not confirmed the superior transduction of HSCs using lentiviral vectors versus oncoretroviral vectors. In contrast to the stable gene marking we have consistently achieved with oncoretroviral vectors in animals that received myeloablative conditioning, we observed the complete disappearance of genetically modified enhanced green or yellow fluorescent protein–expressing cells in 5 baboons that received transplants of HSCs transduced with lentiviral vectors alone or in combination with oncoretroviral vectors. Immune responses to transgene products have been found to be involved in the disappearance of gene-modified cells after nonmyeloablative conditioning. Thus, we examined whether the disappearance of genemodified cells after ablative conditioning may be due to an immune response. In 4 of 5 animals, cytotoxic T lymphocytes specific for the transgene protein were readily detected, demonstrating that immune reactions were responsible for the disappearance of the gene-marked cells in the animals. In summary, we report the induction of transgene-specific immune responses after transplantation of lentivirally transduced repopulating cells in a myeloablative setting. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Transgene-specific tolerance versus immune response Robert E. Donahue, Irvin S. Y. Chen, Julia C. Morris, and Hans-Peter Kiem Blood 2004 104: 1578-1579. [Full Text] [PDF] This article has been cited by other articles: Y.-J. Kim, Y.-S. Kim, A. Larochelle, G. Renaud, T. G. Wolfsberg, R. Adler, R. E. Donahue, P. Hematti, B.-K. Hong, J. Roayaei, et al. Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector-transduced CD34+ cells Blood, May 28, 2009; 113(22): 5434 - 5443. [Abstract] [Full Text] [PDF] K. Lore, R. Seggewiss, F. J. Guenaga, S. Pittaluga, R. E. Donahue, A. Krouse, M. E. Metzger, R. A. Koup, C. Reilly, D. C. Douek, et al. In Vitro Culture During Retroviral Transduction Improves Thymic Repopulation and Output After Total Body Irradiation and Autologous Peripheral Blood Progenitor Cell Transplantation in Rhesus Macaques Stem Cells, June 1, 2006; 24(6): 1539 - 1548. [Abstract] [Full Text] [PDF] J. Tolar, M. J. O'Shaughnessy, A. Panoskaltsis-Mortari, R. T. McElmurry, S. Bell, M. Riddle, R. S. McIvor, S. R. Yant, M. A. Kay, D. Krause, et al. Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells Blood, May 15, 2006; 107(10): 4182 - 4188. [Abstract] [Full Text] [PDF] T. Kalina, H. Lu, Z. Zhao, E. Blewett, D. P. Dittmer, J. Randolph-Habecker, D. G. Maloney, R. G. Andrews, H.-P. Kiem, and J. Storek De novo generation of CD4 T cells against viruses present in the host during immune reconstitution Blood, March 15, 2005; 105(6): 2410 - 2414. [Abstract] [Full Text] [PDF] R. E. Donahue, I. S. Y. Chen, J. C. Morris, and H.-P. Kiem Transgene-specific tolerance versus immune response Blood, September 1, 2004; 104(5): 1578 - 1579. [Full Text] [PDF] H. Hanawa, P. Hematti, K. Keyvanfar, M. E. Metzger, A. Krouse, R. E. Donahue, S. Kepes, J. Gray, C. E. Dunbar, D. A. Persons, et al. Efficient gene transfer into rhesus repopulating hematopoietic stem cells using a simian immunodeficiency virus-based lentiviral vector system Blood, June 1, 2004; 103(11): 4062 - 4069. [Abstract] [Full Text] [PDF] P. A. Horn, K. A. Keyser, L. J. Peterson, T. Neff, B. M. Thomasson, J. Thompson, and H.-P. Kiem Efficient lentiviral gene transfer to canine repopulating cells using an overnight transduction protocol Blood, May 15, 2004; 103(10): 3710 - 3716. [Abstract] [Full Text] [PDF]

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