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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3192-3201. Prepublished online as a Blood First Edition Paper on July 6, 2007; DOI 10.1182/blood-2007-06-094615. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-06-094615v1 110/9/3192    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 Litzinger, M. T. Articles by Palena, C. Search for Related Content PubMed PubMed Citation Articles by Litzinger, M. T. Articles by Palena, C. Related Collections Immunobiology Immunotherapy Chemokines, Cytokines, and Interleukins Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity Mary T. Litzinger1, Romaine Fernando1, Tyler J. Curiel2, Douglas W. Grosenbach1, Jeffrey Schlom1, and Claudia Palena1 1 Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; 2 San Antonio Cancer Institute, The University of Texas Health Science Center at San Antonio CD4+CD25+Foxp3+ regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity. Denileukin diftitox (DAB389IL-2), a fusion protein of interleukin 2 (IL-2) and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (1) the effect of denileukin diftitox on the deletion of Treg cells in various lymphoid compartments and (2) the dose scheduling of denileukin diftitox in combination with a recombinant poxviral vaccine to enhance antigen-specific immune responses. Treg cells in spleen, peripheral blood, and bone marrow of normal C57BL/6 mice were variously reduced after a single intraperitoneal injection of denileukin diftitox; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of denileukin diftitox 1 day before vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies show for the first time in a murine model (1) the differential effects of denileukin diftitox on Treg cells in different cellular compartments, (2) the advantage of combining denileukin diftitox with a vaccine to enhance antigen-specific T-cell immune responses, (3) the lack of inhibition by denileukin diftitox of host immune responses directed against a live viral vector, and (4) the importance of dose scheduling of denileukin diftitox when used in combination with a vaccine. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Treg cells, cancer vaccines: timing is everything Pawel Kalinski Blood 2007 110: 3090-3091. [Full Text] [PDF] This article has been cited by other articles: L. Gil-Guerrero, J. Dotor, I. L. Huibregtse, N. Casares, A. B. Lopez-Vazquez, F. Rudilla, J. I. Riezu-Boj, J. Lopez-Sagaseta, J. Hermida, S. Van Deventer, et al. In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-{beta}1 J. Immunol., July 1, 2008; 181(1): 126 - 135. [Abstract] [Full Text] [PDF] 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]

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