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Keywords:

  • bladder;
  • bladder carcinoma;
  • mice;
  • interleukin-23;
  • gene therapy

OBJECTIVES

  • • 
    To evaluate the antitumour effects of IL-23 gene transfer into mouse bladder carcinoma (MBT2) cells.
  • • 
    To investigate the mechanisms underlying the subsequent constitutive secrection of IL-23 by the MBT2 cells

MATERIALS AND METHODS

  • • 
    An expression vector containing IL-23 gene was introduced into MBT2 cells by liposome-mediated gene transfer, and secretion of IL-23 was confirmed by ELISA.
  • • 
    The in vivo antitumour effect of IL-23-secreting MBT2 cells (MBT2/IL-23) was examined by injecting the cells into syngeneic C3H mice.
  • • 
    A tumour vaccination study using mitomycin C (MMC)-treated IL-23-secreting MBT2 cells was carried out, and the usefulness of in vivo CD25 depletion for an additional vaccine effect was also investigated.
  • • 
    The mechanisms underlying the antitumour effects were investigated by antibody depletion of CD8 or CD4 T cells, or natural killer cells, and cells infiltrating the tumour sites in vivo were assessed using immunohistochemistry.

RESULTS

  • • 
    Stable transformants transduced with MBT2/IL-23 secreted IL-23 into the culture supernatant.
  • • 
    Genetically engineered IL-23-secreting MBT2 cells were rejected in syngeneic mice.
  • • 
    MBT2/IL-23-vaccinated mice inhibited the tumour growth of parental MBT2 cells injected at a distant site and this vaccine effect was enhanced by combination with in vivo CD25 depletion by an antibody.
  • • 
    The main effector cells for the direct antitumour effect of MBT2/IL-23 were CD8 T cells, which was shown by in vivo depletion and immunohistochemical study.

CONCLUSIONS

  • • 
    IL-23-secreting MBT2 cells were rejected in syngeneic mice by the activation of CD8 T cells.
  • • 
    MMC-treated MBT2/IL-23 can have a tumour vaccine effect for parental MBT2 cells, and this effect was enhanced by combination with in vivo CD25 depletion.