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.