RRC ID 1913
Author Iinuma H, Okinaga K, Fukushima R, Inaba T, Iwasaki K, Okinaga A, Takahashi I, Kaneko M.
Title Superior protective and therapeutic effects of IL-12 and IL-18 gene-transduced dendritic neuroblastoma fusion cells on liver metastasis of murine neuroblastoma.
Journal J. Immunol.
Abstract Fusion vaccine of dendritic cells (DCs) and tumor cells has the advantage of inducing an immune response against multiple tumor Ags, including unknown tumor Ags. Using the liver metastasis model of C1300 neuroblastoma cells, we assessed the protective and therapeutic effects of fusion cells transduced with the IL-12 gene and/or the IL-18 gene. Improving the fusion method by combining polyethylene glycol and electroporation increased loading efficiency. In the A/J mice vaccinated with fusion cells modified with the LacZ gene (fusion/LacZ), IFN-gamma production and CTL activity increased significantly compared with that of DCs/LacZ, C1300/LacZ, or a mixture of the two (mixture/LacZ). With the transduction of IL-12 and IL-18 genes into the fusion cells (fusion/IL-12/IL-18), the level of IFN-gamma increased more than five times that of other fusion groups. In addition, NK cell activity and CTL activity increased significantly compared with that of mixture/LacZ, fusion/LacZ, DC/LacZ, or C1300/LacZ. In the protective and therapeutic studies of fusion cell vaccine, mice vaccinated with fusion/LacZ, fusion/IL-12, fusion/IL-18, or fusion/IL-12/IL-18 showed a significant decrease in liver metastasis and a significant increase in survival compared with mice given a mixture/LacZ, DCs/LacZ, or C1300/LacZ. In particular, the mice receiving fusion/IL-12/IL-18 vaccine showed a complete protective effect and the highest therapeutic effects. The present study investigates the improved loading efficiency of fusion cells and suggests that the introduction of IL-12 and IL-18 genes can induce extremely strong protective and therapeutic effects on liver metastasis of neuroblastoma.
Volume 176(6)
Pages 3461-9
Published 2006-3-15
DOI 10.4049/jimmunol.176.6.3461
PII 176/6/3461
PMID 16517714
MeSH Animals Cell Fusion Cell Line Cell- and Tissue-Based Therapy Dendritic Cells / cytology* Dendritic Cells / metabolism Female Genetic Therapy Immunization Interleukin-12 / biosynthesis Interleukin-12 / genetics Interleukin-12 / metabolism* Interleukin-18 / biosynthesis Interleukin-18 / genetics Interleukin-18 / metabolism* Killer Cells, Natural / immunology Killer Cells, Natural / metabolism Liver Neoplasms / genetics Liver Neoplasms / immunology Liver Neoplasms / secondary* Liver Neoplasms / therapy* Mice Neoplasm Transplantation Neuroblastoma / genetics* Neuroblastoma / immunology Neuroblastoma / pathology* Neuroblastoma / therapy Phenotype Spleen / metabolism Survival Rate T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Cytotoxic / metabolism
IF 4.718
Times Cited 42
Human and Animal Cells YAC-1