Intravesical interleukin-15 gene therapy in an orthotopic bladder cancer model

Kazuhiro Matsumoto, Eiji Kikuchi, Minoru Horinaga, Toshikazu Takeda, Akira Miyajima, Ken Nakagawa, Mototsugu Oya

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19 Citations (Scopus)

Abstract

Interleukin-15 (IL-15) is known to stimulate the proliferation of CD8 + T-cells and natural killer cells, and also to help to maintain memory CD8 + T cells, suggesting that it may be of value in cytokine treatment of bladder cancer. In this experiment, we tested the efficiency of intravesical liposomal IL-15 gene delivery and its antitumor effect in a mouse orthotopic bladder cancer model. We established an orthotopic bladder cancer model by implanting 5×10 5 MBT-2 cells into female C3H/HeN mice through the urethra. The mice received repeated intravesical gene delivery injected with liposome-mediated plasmids (5μg) transurethrally. On day 23, the bladder weights in the group receiving medium alone, the beta-galactosidase gene delivery control group, and the IL-15 gene therapy group were 196±36mg, 201±35mg, and 96±29mg, respectively (p<0.05), demonstrating the antitumor effect of intravesical IL-15 gene therapy in this model. In the bladders treated with IL-15 gene plasmid instillation, histological analysis revealed that many inflammatory cells were induced around the tumors. Immunohistochemical analysis confirmed that there was predominant infiltration of CD8 + T cells around the tumor nest. After the intravesical IL-15 gene therapy, the growth of rechallenged subcutaneous MBT-2 cells in surviving mice was inhibited again via tumor-specific cytotoxic T lymphocytes, although newly implanted FM3A cells in the same mice were not rejected. The present findings indicate that IL-15 gene therapy may be a promising new adjuvant therapy for bladder cancer.

Original languageEnglish
Pages (from-to)1423-1432
Number of pages10
JournalHuman Gene Therapy
Volume22
Issue number11
DOIs
Publication statusPublished - 2011 Nov 1

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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