Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage-colony stimulating factor and interleukin-2 surface modified MB49 bladder cancer stem cells vaccine

Abstract

In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated. The therapeutic, protective, specific, and memorial immune response animal experiments were designed. Tumor-specific cytotoxic T lymphocytes assay, enzyme linked immunosorbent assay, flow cytometry assay were performed to indentify whether vaccine caused an antitumor immunity. Streptavidin (SA)-GM-CSF and SA-IL-2 MCSCs vaccines were prepared successfully. Such vaccines inhibited the volume of tumor and prolonged the survival of the mice in animal experiments. The express of IgG or IFN-c, the portion of dendritic cells, CD8+ and CD4+ T cells were highest in the combined vaccines group than the SA-GM-CSF vaccine group, the SA-IL-2 vaccine group, the MCSCs group and the PBS group. The combined of GM-CSF and IL-2 vaccines could induce better antitumor immunity than a vaccine alone.