Abstract
Dendritic cells (DC) manipulated ex vivo can induce tumor immunity in experimental murine tumor models. To improve DC-based tumor vaccination, we studied whether DC maturation affects the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4 alone or by further addition of TNF-alpha or a cytidine-phosphate-guanosine (CpG)-containing oligonucleotide (ODN-1826), which mimics the immunostimulatory effect of bacterial DNA. Flow cytometric analysis of costimulatory molecules and MHC class II showed that DC maturation was stimulated most by ODN-1826, whereas TNF-alpha had an intermediate effect. The extent of maturation correlated with the secretion of IL-12 and the induction of alloreactive T cell proliferation. In BALB/c mice, s.c. injection of colon carcinoma cells resulted in rapidly growing tumors. In this model, CpG-ODN-stimulated DC cocultured with irradiated tumor cells also induced prophylactic protection most effectively and were therapeutically effective when administered 3 days after tumor challenge. Thus, CpG-ODN-enhanced DC maturation may represent an efficient means to improve clinical tumor vaccination.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Adjuvants, Immunologic / therapeutic use
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Animals
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Antineoplastic Agents / immunology*
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Antineoplastic Agents / therapeutic use
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Cell Communication / immunology
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Cell Differentiation / immunology
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Cells, Cultured
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Coculture Techniques
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Colonic Neoplasms / immunology
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Colonic Neoplasms / pathology
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Colonic Neoplasms / prevention & control
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CpG Islands / immunology*
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / transplantation
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Female
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Growth Inhibitors / immunology
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Growth Inhibitors / therapeutic use
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Immunotherapy, Adoptive / methods
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Interleukin-12 / biosynthesis
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Interleukin-4 / pharmacology
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Neoplasm Transplantation
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Oligodeoxyribonucleotides / immunology*
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Oligodeoxyribonucleotides / therapeutic use
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T-Lymphocytes / immunology*
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Tumor Cells, Cultured / immunology
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Tumor Cells, Cultured / transplantation
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Tumor Necrosis Factor-alpha / immunology*
Substances
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Adjuvants, Immunologic
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Antineoplastic Agents
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CPG-oligonucleotide
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Growth Inhibitors
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Oligodeoxyribonucleotides
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Tumor Necrosis Factor-alpha
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Interleukin-12
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Interleukin-4