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

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 3alpha, and they che...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-12, Vol.167 (11), p.6644-6653
Main Authors: Biragyn, Arya, Surenhu, Munhsuren, Yang, De, Ruffini, Pier Adelchi, Haines, Bryan Allen, Klyushnenkova, Elena, Oppenheim, Joost J, Kwak, Larry W
Format: Article
Language:English
Subjects:
Animals
Antibodies, Anti-Idiotypic - biosynthesis
Antibodies, Anti-Idiotypic - genetics
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
beta-Defensins - administration & dosage
beta-Defensins - genetics
beta-Defensins - immunology
beta-Defensins - physiology
Cancer Vaccines - administration & dosage
Cancer Vaccines - genetics
Cancer Vaccines - immunology
CCL2 protein
CCR6 protein
Cell Differentiation - genetics
Cell Differentiation - immunology
Cell Line
Chemokines - administration & dosage
Chemokines - genetics
Chemokines - immunology
Chemokines - physiology
CXCL2 protein
Dendritic Cells - cytology
Dendritic Cells - immunology
Female
Gene Targeting
Humans
Immunity, Innate - genetics
Immunoglobulin Variable Region - administration & dosage
Immunoglobulin Variable Region - genetics
Immunoglobulin Variable Region - immunology
Immunotherapy, Adoptive - methods
Lymphoma, B-Cell - genetics
Lymphoma, B-Cell - immunology
Lymphoma, B-Cell - therapy
macrophage inflammatory protein 3^a
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Receptors, Chemokine - genetics
Recombinant Fusion Proteins - administration & dosage
Recombinant Fusion Proteins - chemical synthesis
Recombinant Fusion Proteins - immunology
Recombinant Fusion Proteins - physiology
stromal cell-derived factor 1
Tumor Cells, Cultured
Vaccines, DNA - administration & dosage
Vaccines, DNA - genetics
Vaccines, DNA - immunology
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Summary: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 3alpha, 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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.167.11.6644