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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2004 Accepted May 16, 2004 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 Laboratory of Immunology, National Institute on Aging, Baltimore, MD, USA Experimental Transplantation and Immunology Branch, National Cancer Institute, Frederick, MD, USA; The Divisione di Oncologia Medica Falck, Ospendale Niguarda Granda, Milan, Italy Experimental Transplantation and Immunology Branch, National Cancer Institute, Frederick, MD, USA; IRSP, SAIC, Frederick, MD, USA; Divisione di Ematologia, Universita di Torino, Laboratorio di Ematologia Oncologica, CeRMS, Azienda Ospedaliera San Giovanni Battista, Torino, Italy IRSP, SAIC, Frederick, MD, USA Experimental Transplantation and Immunology Branch, National Cancer Institute, Frederick, MD, USA Laboratory of Immunoregulation, National Cancer Institute, Frederick, MD, USA * Corresponding author; email: biragyna{at}grc.nia.nih.gov. Non-immunogenic antigens can be efficiently rendered immunogenic by targeting them to APC via differentially expressed chemokine receptors. For example, self-tumor or HIV antigens genetically fused with proinflammatory chemo-attractants 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 MHC class II pathway. Experiments with inhibitors of intracellular trafficking suggest that chemo-attractant fusion proteins, but not antigen alone, were processed and presented through early/late endosomal and Golgi compartments, and stimulate antigen-specific CD4+ T cells both in vitro and in vivo. Chemokine fusion also facilitated the presentation of antigen by DC 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 anti-host chemokine autoimmunity, for example, by use of viral chemo-attractants 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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