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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1278-1285. Prepublished online as a Blood First Edition Paper on May 5, 2005; DOI 10.1182/blood-2005-01-0318. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 2005-01-0318v1 106/4/1278    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 Tacken, P. J. Articles by Figdor, C. G. Search for Related Content PubMed PubMed Citation Articles by Tacken, P. J. Articles by Figdor, C. G. Related Collections Immunobiology Cell Adhesion and Motility Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti–DC-SIGN antibody Paul J. Tacken, I. Jolanda M. de Vries, Karlijn Gijzen, Ben Joosten, Dayang Wu, Russell P. Rother, Susan J. Faas, Cornelis J. A. Punt, Ruurd Torensma, Gosse J. Adema, and Carl G. Figdor From the Departments of Tumor Immunology, Pediatric Oncology, and Medical Oncology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and Alexion Pharmaceuticals, Cheshire, CT. Current dendritic cell (DC)–based vaccines are based on ex vivo–generated autologous DCs loaded with antigen prior to readministration into patients. A more direct and less laborious strategy is to target antigens to DCs in vivo via specific surface receptors. Therefore, we developed a humanized antibody, hD1V1G2/G4 (hD1), directed against the C-type lectin DC-specific intercellular adhesion molecule 3–grabbing nonintegrin (DC-SIGN) to explore its capacity to serve as a target receptor for vaccination purposes. hD1 was cross-linked to a model antigen, keyhole limpet hemocyanin (KLH). We observed that the chimeric antibody-protein complex (hD1-KLH) bound specifically to DC-SIGN and was rapidly internalized and translocated to the lysosomal compartment. To determine the targeting efficiency of hD1-KLH, monocyte-derived DCs and peripheral blood lymphocytes (PBLs) were obtained from patients who had previously been vaccinated with KLH-pulsed DCs. Autologous DCs pulsed with hD1-KLH induced proliferation of patient PBLs at a 100-fold lower concentration than KLH-pulsed DCs. In addition, hD1-KLH–targeted DCs induced proliferation of naive T cells recognizing KLH epitopes in the context of major histocompatibility complex (MHC) classes I and II. We conclude that antibody-mediated targeting of antigen to DCs via DC-SIGN effectively induces antigen-specific naive as well as recall T-cell responses. This identifies DC-SIGN as a promising target molecule for DC-based vaccination strategies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Wei, S. Wang, D. Zhang, S. Hou, W. Qian, B. Li, H. Guo, G. Kou, J. He, H. Wang, et al. Targeted Delivery of Tumor Antigens to Activated Dendritic Cells via CD11c Molecules Induces Potent Antitumor Immunity in Mice Clin. Cancer Res., July 15, 2009; 15(14): 4612 - 4621. [Abstract] [Full Text] [PDF] P. Krause, M. Bruckner, C. Uermosi, E. Singer, M. Groettrup, and D. F. 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