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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2294-2302. Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-08-3503. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3503v1 107/6/2294    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 Berger, C. Articles by Riddell, S. R. Search for Related Content PubMed PubMed Citation Articles by Berger, C. Articles by Riddell, S. R. Related Collections Immunobiology Transplantation Immunotherapy Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY 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 Carolina Berger, Mary E. Flowers, Edus H. Warren, and Stanley R. Riddell From the Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA; and the University of Washington, Department of Medicine, Seattle. The introduction of an inducible suicide gene such as the herpes simplex virus thymidine kinase (HSV-TK) might allow exploitation of the antitumor activity of donor T cells after allogeneic hematopoietic cell transplantation (HCT) without graft versus host disease. However, HSV-TK is foreign, and immune responses to gene-modified T cells could lead to their premature elimination. We show that after the infusion of HSV-TK–modified donor T cells to HCT recipients, CD8+ and CD4+ T-cell responses to HSV-TK are rapidly induced and coincide with the disappearance of transferred cells. Cytokine flow cytometry using an overlapping panel of HSV-TK peptides allowed rapid detection and quantitation of HSV-TK–specific T cells in the blood and identified multiple immunogenic epitopes. Repeated infusion of modified T cells boosted the induced HSV-TK–specific T cells, which persisted as memory cells. These studies demonstrate the need for nonimmunogenic suicide genes and identify a strategy for detection of CD4+ and CD8+ T-cell responses to transgene products that should be generally applicable to monitoring patients on gene therapy trials. The potency of gene-modified T cells to elicit robust and durable immune responses imply this approach might be used for vaccination to elicit T-cell responses to viral or tumor antigens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Suicide is painless Helen E. Heslop Blood 2006 107: 2211-2212. [Full Text] [PDF] This article has been cited by other articles: R. Fontana, M. Bregni, A. Cipponi, L. Raccosta, C. Rainelli, D. Maggioni, F. Lunghi, F. Ciceri, S. Mukenge, C. Doglioni, et al. Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients Blood, February 19, 2009; 113(8): 1651 - 1660. [Abstract] [Full Text] [PDF] C. J. Shu, C. G. Radu, S. M. Shelly, D. D. Vo, R. Prins, A. Ribas, M. E. Phelps, and O. N. Witte Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen Int. Immunol., February 1, 2009; 21(2): 155 - 165. [Abstract] [Full Text] [PDF] M. A. de Witte, A. Jorritsma, E. Swart, K. C. Straathof, K. de Punder, J. B. A. G. Haanen, C. M. Rooney, and T. N. M. Schumacher An Inducible Caspase 9 Safety Switch Can Halt Cell Therapy-Induced Autoimmune Disease J. Immunol., May 1, 2008; 180(9): 6365 - 6373. [Abstract] [Full Text] [PDF] E. Kieback, J. Charo, D. Sommermeyer, T. Blankenstein, and W. Uckert A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer PNAS, January 15, 2008; 105(2): 623 - 628. [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] M. J. Pittet, J. Grimm, C. R. Berger, T. Tamura, G. Wojtkiewicz, M. Nahrendorf, P. Romero, F. K. Swirski, and R. Weissleder In vivo imaging of T cell delivery to tumors after adoptive transfer therapy PNAS, July 24, 2007; 104(30): 12457 - 12461. [Abstract] [Full Text] [PDF] P. Tiberghien Altruistic donor T cells Blood, June 1, 2007; 109(11): 4595 - 4595. [Full Text] [PDF] C. Traversari, S. Marktel, Z. Magnani, P. Mangia, V. Russo, F. Ciceri, C. Bonini, and C. Bordignon The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies Blood, June 1, 2007; 109(11): 4708 - 4715. [Abstract] [Full Text] [PDF] 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]

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