An experimental study of dendritic cell-based vaccine therapy for intracranial gliomas

Objective:To investigate the therapeutic efficacy of immunotherapy with dendritic cells-based vaccine against intracranial gliomas in rats.Methods:C6 glioma cells were injected into the brain of Wistar rat under stereotactic monitor to establish an animal model of glioma.The precursors of dendritic cells were isolated from bone marrow of rats,stimulated in vitro with recombinant rat granulocyte-macrophage colony-stimulating factor(rrGM-CSF)and interleukin-4(rrIL-4).Cultured cell populations were confirmed to be functional DCs.These DCs were then pulsed ex vivo with C6 tumor-lysates prepared by three cycles of freezing to -80℃ and thawing to 0℃ and subsequently injected subcutaneously into rats harboring intracranial C6 tumor.Rats from different group were treated with five weekly subcutaneous injections of either control media,unpulsed DCs,or DCs pulsed with tumor-lysates.The animals were followed for survival,the percentage of CD8 +T cells in peripheral blood and cytotoxicity assay in vitro were determined by FACS.The level of cytokine IFN-γ and IL-10 were detected by ELISA.Results:The results indicated that C6 glioma model rats treated with tumor-lysate-pulsed DCs led to prolonged survival time,increased the percentage of CD8 + T lymphocyte in peripheral blood in comparing with control group.Cytotoxicity assays suggest that vaccination with these tumor-lysate-pulsed DCs can induce specific cytotoxic T lymphocytes against C6 tumor cells compared with control group.Furthermore,significantly enhanced IFN-γ and reduced IL-10 (even undetectable)were observed in rats treated with pulsed-DCs.Conclusion:Data supported the therapeutic efficacy of systemic vaccination with DCs pulsed with tumor-lysates against intracranial glioma.