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The Journal of Immunology, 2001, 167: 6644-6653.
Copyright © 2001 by The American Association of Immunologists

Mediators of Innate Immunity That Target Immature, But Not Mature, Dendritic Cells Induce Antitumor Immunity When Genetically Fused with Nonimmunogenic Tumor Antigens

Arya Biragyn1,*, Munhsuren Surenhu*,{dagger}, De Yang{dagger},{ddagger}, Pier Adelchi Ruffini2,*, Bryan Allen Haines*, Elena Klyushnenkova*,{dagger}, Joost J. Oppenheim{ddagger} and Larry W. Kwak*

* Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892; and {dagger} Science Application International Corp. and {ddagger} Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702

Chemokine receptors are differentially expressed on immature and mature dendritic cells (DC). 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 humoral, protective, and therapeutic immunity against two different syngeneic lymphomas.




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