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RESEARCH PRODUCT
Enhanced dendritic cell maturation by TNF-alpha or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo.
Wolfgang HaimerlChristoph BrunnerJulia SeidererGunther HartmannArthur M. KriegArthur M. KriegArthur M. KriegHans-anton LehrStefan EndresMartin BidlingmaierAndreas EiglerAngelika Schlampsubject
T cellT-LymphocytesImmunologyAntineoplastic AgentsCell CommunicationBiologyLymphocyte ActivationImmunotherapy AdoptiveMiceImmune systemAdjuvants ImmunologicIn vivomedicineTumor Cells CulturedImmunology and AllergyAnimalsInterleukin 4Cells CulturedMice Inbred BALB CTumor Necrosis Factor-alphaCell DifferentiationDendritic cellDendritic CellsMolecular biologyInterleukin-12Coculture TechniquesGrowth InhibitorsMice Inbred C57BLmedicine.anatomical_structureOligodeoxyribonucleotidesColonic NeoplasmsInterleukin 12Cancer researchTumor necrosis factor alphaCpG IslandsFemaleInterleukin-4Ex vivoNeoplasm Transplantationdescription
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-α 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-α 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2000-12-01 | Journal of immunology (Baltimore, Md. : 1950) |