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

Dendritic cells (DC) manipulated ex vivo can induce tumor immunity in exper imental murine tumor models. To improve DC-based tumor vaccination, we stud ied whether DC maturation affects the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Maturation of murine bone marr ow-derived DC was induced by GM-CSF plus IL-4 alone or by further addition of TNF-ar or a cytidine-phosphate-guanosine (CpG)-containing oligonucleotid e (ODN-1826), which mimics the immunostimulatory effect of bacterial DNA, F low cytometric analysis of costimulatory molecules and MHC class II showed that DC maturation was stimulated most by ODN-1826, whereas TNF-alpha had a n intermediate effect, The extent of maturation correlated with the secreti on 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 growin g tumors. In this model, CpG-ODN-stimulated DC cocultured with irradiated t umor cells also induced prophylactic protection most effectively and were t herapeutically effective when administered 3 days after tumor challenge. Th us, CpG-ODN-enhanced DC maturation may represent an efficient means to impr ove clinical tumor vaccination.