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IL‐23 gene therapy for mouse bladder tumour cell lines
Author(s) -
Kuramoto Tomomi,
Fujii Reona,
Nagai Hiroshi,
Belladonna Maria Laura,
Yoshimoto Takayuki,
Kohjimoto Yasuo,
Inagaki Takeshi,
Hara Isao
Publication year - 2011
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2010.10025.x
Subject(s) - in vivo , cd8 , genetic enhancement , antibody , il 2 receptor , biology , interleukin 12 , cancer research , cell culture , microbiology and biotechnology , cytotoxic t cell , in vitro , immunology , immune system , t cell , gene , biochemistry , genetics
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 cellsMATERIALS 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.