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Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens

  1. Author:
    Biragyn, A.
    Surenhu, M.
    Yang, D.
    Ruffini, P. A.
    Haines, B. A.
    Klyushnenkova, E.
    Oppenheim, J. J.
    Kwak, L. W.

  2. Author Address

    NCI, Mol Immunoregulat Lab, Bldg 567, Room 213, Frederick, MD 21702 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Mclean, VA 22102 USA. Biragyn A NCI, Mol Immunoregulat Lab, Bldg 567, Room 213, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Journal of Immunology
    1. 167
    2. 11
    3. Pages: 6644-6653
  4. Type of Article: Article
  1. Abstract:

    Chemokine receptors are differentially expressed on immature and mature dendritic cells (DQ. Herein, we demonstrate for the first time that murine antimicrobial peptides beta -defensins 2 and 3 bind murine CCR6, similarly to inflammatory chemokine macrophage-inflammatory protein 3 alpha, and they chemoattract bone marrow-derived immature, but not mature DC. Using various chemokines or defensins fused with nonimmunogenic tumor Ags, we studied their capacity to delivery Ags to subsets of immune cells to elicit antitumor immunity. We demonstrate that DNA immunizations with fusion constructs with beta -defensin 2 or inflammatory chemokines that target immature DC, but not homeostatic chemokines secondary lymphoid tissue chemokine, CCL21, or stromal cell-derived factor 1, CXCL12, which chemoattract mature DC, elicit Immoral, protective, and therapeutic immunity against two different syngeneic lymphomas.

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