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Blood, 1 October 2004, Vol. 104, No. 7, pp. 1961-1969. Prepublished online as a Blood First Edition Paper on June 10, 2004; DOI 10.1182/blood-2004-02-0637. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0637v1 104/7/1961    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 Biragyn, A. Articles by Kwak, L. W. Search for Related Content PubMed PubMed Citation Articles by Biragyn, A. Articles by Kwak, L. W. 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  CHEMOKINES Chemokine receptor-mediated delivery directs self-tumor antigen efficiently into the class II processing pathway in vitro and induces protective immunity in vivo Arya Biragyn, Pier Adelchi Ruffini, Marta Coscia, Linda K. Harvey, Sattva S. Neelapu, Sivasubramanian Baskar, Ji-Ming Wang, and Larry W. Kwak From the Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, Baltimore, MD; Experimental Transplantation and Immunology Branch, Laboratory of Immunoregulation, National Cancer Institute, Frederick, MD; Department of Lymphoma/Myeloma, M.D. Anderson Cancer Center, Houston, TX; Intramural Research Support Program, Science Applications International Corporation (IRSP SAIC)–Frederick, Frederick, MD; and Divisione di Oncologia Medica Falck, Ospedale Niguarda Ca' Granda, Milan, Italy. Nonimmunogenic antigens can be efficiently rendered immunogenic by targeting them to antigen-presenting cells via differentially expressed chemokine receptors. For example, self-tumor or HIV antigens genetically fused with proinflammatory chemoattractants elicit potent immune responses and protective antitumor immunity in mice. Herein we demonstrate that the mechanism by which chemokine fusions elicit responses is efficient uptake, processing, and presentation of antigens via the major histocompatibility complex class II pathway. Experiments with inhibitors of intracellular trafficking suggest that chemoattractant fusion proteins, but not antigen alone, were processed and presented through early/late endosomal and Golgi compartments and stimulated antigen-specific CD4+ T cells both in vitro and in vivo. Chemokine fusion also facilitated the presentation of antigen by dendritic cells to an autologous human tumor-specific CD4+ T-cell line. Taking advantage of chemokine redundancy, viral chemokine fusions were equally potent in inducing protective immunity in vivo, providing a possible strategy to circumvent hypothetical, vaccine-induced antihost chemokine autoimmunity, for example, by use of viral chemoattractants in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The APC's of tumor vaccine therapy Scott S. Zamvil and Thomas Prod'homme Blood 2004 104: 1915-1916. [Full Text] [PDF] This article has been cited by other articles: A. B. Fredriksen and B. Bogen Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences Blood, September 15, 2007; 110(6): 1797 - 1805. [Abstract] [Full Text] [PDF] D. Baatar, P. Olkhanud, D. Newton, K. Sumitomo, and A. Biragyn CCR4-Expressing T Cell Tumors Can Be Specifically Controlled via Delivery of Toxins to Chemokine Receptors J. Immunol., August 1, 2007; 179(3): 1996 - 2004. [Abstract] [Full Text] [PDF] A. Biragyn, R. Schiavo, P. Olkhanud, K. Sumitomo, A. King, M. McCain, F. E. Indig, G. Almanzar, and D. Baatar Tumor-Associated Embryonic Antigen-Expressing Vaccines that Target CCR6 Elicit Potent CD8+ T Cell-Mediated Protective and Therapeutic Antitumor Immunity J. Immunol., July 15, 2007; 179(2): 1381 - 1388. [Abstract] [Full Text] [PDF] R. Schiavo, D. Baatar, P. Olkhanud, F. E. Indig, N. Restifo, D. Taub, and A. Biragyn Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses Blood, June 15, 2006; 107(12): 4597 - 4605. [Abstract] [Full Text] [PDF] J. J. Oppenheim, H. F. Dong, P. Plotz, R. R. Caspi, M. Dykstra, S. Pierce, R. Martin, C. Carlos, O. Finn, O. Koul, et al. Autoantigens act as tissue-specific chemoattractants J. Leukoc. Biol., June 1, 2005; 77(6): 854 - 861. [Abstract] [Full Text] [PDF]

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