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.

PD‐1 blockade enhances the antitumor efficacy of GM‐CSF surface‐modified bladder cancer stem cells vaccine

“…Our previous study demonstrated that the GM-CSF-modified MCSCs vaccine could significantly promote the uptake of tumor-associated antigens by the immune system and enhance the immunogenicity of tumor cells, tumor-specific CTL activity, and in vivo antitumor responses. [6][7][8] The results of our study also showed that more mature DCs were detected in the spleen of mice treated with the MCSCs vaccine. However, although this vaccination approach induced unprecedentedly strong CD8 1 T-cell responses and CD4 1 T-cell responses, this effect was usually restricted to the early stages of tumor growth.…”

“…Through our protein–anchor platform, the proposed MCSCs vaccine not only contained all of the tumor‐associated antigens but also maintained the activity of cytokines to enhance the immunogenicity of the vaccine. Our previous study demonstrated that the GM‐CSF‐modified MCSCs vaccine could significantly promote the uptake of tumor‐associated antigens by the immune system and enhance the immunogenicity of tumor cells, tumor‐specific CTL activity, and in vivo antitumor responses . The results of our study also showed that more mature DCs were detected in the spleen of mice treated with the MCSCs vaccine.…”

“…We previously developed granulocyte‐macrophage‐colony stimulating factor (GM‐CSF) surface‐modified CSCs vaccine to induce specific immune response for eliminating CSCs . GM‐CSF is a cytokine that promotes the growth and maturation of DCs and initiates the immune response .…”

“…6 We previously developed granulocyte-macrophage-colony stimulating factor (GM-CSF) surface-modified CSCs vaccine to induce specific immune response for eliminating CSCs. [6][7][8] GM-CSF is a cytokine that promotes the growth and maturation of DCs and initiates the immune response. 9 Although the therapeutic CSCs vaccine could significantly enhance dendritic cells (DCs) activation, tumor-specific cytotoxic Tlymphocyte activity, and antitumor responses in vivo, this effect is usually restricted to the early stages of tumor growth.…”

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells

“…Following GVAX inoculation, sustained local release of GM-CSF significantly increased levels of M1 macrophages, dendritic cell populations, and CD8 + T cells, exerting antitumor immunity effects [ 170 ]. In addition, the IL-2 vaccine can also induce specific antitumor immunity in mice, and the combination of GVAX and IL-2 vaccine was noted to have better antitumor effects than the single treatment [ 171 ]. These results suggest that GVAX can induce strong tumor immunity and can be used in tumor immunotherapy.…”