4.6 Article

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

期刊

CANCER MEDICINE
卷 6, 期 3, 页码 689-697

出版社

WILEY
DOI: 10.1002/cam4.1023

关键词

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

类别

资金

  1. Natural Science Foundation of Guangdong Province [2016A030310403]
  2. Medical Scientific Research Foundation of Guangdong Province [A2016092]
  3. Chinese Medical Association of Clinical Medicine Research Special Fund [16020530669]
  4. Merck Serono China Research Fund

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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.

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