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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 8, 2007 Accepted July 2, 2007 The IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity Mary T Litzinger, Romaine Fernando, Tyler J. Curiel, Douglas W. Grosenbach, Jeffrey Schlom*, and Claudia Palena Laboratory of Tumor Immunology & Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States San Antonio Cancer Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States * Corresponding author; email: js141c{at}nih.gov. CD4+CD25+Foxp3+ regulatory T (Treg) cells have been implicated in the lack of effective anti-tumor immunity. Denileukin diftitox (DAB389IL-2, ONTAK), a fusion protein of IL-2 and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (a) the effect of ONTAK on the deletion of Treg cells in various lymphoid compartments and (b) the dose scheduling of ONTAK 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 ONTAK; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of ONTAK 1 day prior to vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies demonstrate for the first time in a murine model (a) the differential effects of ONTAK on Tregs in different cellular compartments, (b) the advantage of combining ONTAK with a vaccine to enhance antigen-specific T-cell immune responses, (c) the lack of inhibition by ONTAK of host immune responses directed against a live viral vector, and (d) the importance of dose scheduling of ONTAK when employed 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: Q. Zhou, C. Bucher, M. E. Munger, S. L. Highfill, J. Tolar, D. H. Munn, B. L. Levine, M. Riddle, C. H. June, D. A. Vallera, et al. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia Blood, October 29, 2009; 114(18): 3793 - 3802. [Abstract] [Full Text] [PDF] G. Gong, L. Shao, Y. Wang, C. Y. Chen, D. Huang, S. Yao, X. Zhan, H. Sicard, R. Wang, and Z. W. Chen Phosphoantigen-activated V{gamma}2V{delta}2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection Blood, January 22, 2009; 113(4): 837 - 845. [Abstract] [Full Text] [PDF] M. S. Wilson, J. T. Pesce, T. R. Ramalingam, R. W. Thompson, A. Cheever, and T. A. Wynn Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells J. Immunol., November 15, 2008; 181(10): 6942 - 6954. [Abstract] [Full Text] [PDF] Q. Jiang, L. Zhang, R. Wang, J. Jeffrey, M. L. Washburn, D. Brouwer, S. Barbour, G. I. Kovalev, D. Unutmaz, and L. Su FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-{gamma}C-/- mice in vivo Blood, October 1, 2008; 112(7): 2858 - 2868. [Abstract] [Full Text] [PDF] R. Trotta, J. D. Col, J. Yu, D. Ciarlariello, B. Thomas, X. Zhang, J. Allard II, M. Wei, H. Mao, J. C. Byrd, et al. TGF-{beta} Utilizes SMAD3 to Inhibit CD16-Mediated IFN-{gamma} Production and Antibody-Dependent Cellular Cytotoxicity in Human NK Cells J. Immunol., September 15, 2008; 181(6): 3784 - 3792. [Abstract] [Full Text] [PDF] M. A. Morse, A. C. Hobeika, T. Osada, D. Serra, D. Niedzwiecki, H. K. Lyerly, and T. M. Clay Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines Blood, August 1, 2008; 112(3): 610 - 618. [Abstract] [Full Text] [PDF] 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. 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