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

Cancer Med. 2017 Mar;6(3):689-697. doi: 10.1002/cam4.1023. Epub 2017 Feb 16.

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.

Keywords: Bladder cancer stem cells; granulocyte macrophage-colony stimulating factor; interleukin-2; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Immunotherapy
  • Interleukin-2 / metabolism*
  • Mice
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / transplantation
  • Treatment Outcome
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Cancer Vaccines
  • Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor