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

Research output: Contribution to journalArticle

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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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Interleukin-15
Urinary Bladder Neoplasms
Genetic Therapy
T-Lymphocytes
Genes
Urinary Bladder
Plasmids
Neoplasms
Inbred C3H Mouse
Cytotoxic T-Lymphocytes
Urethra
beta-Galactosidase
Liposomes
Natural Killer Cells
Cytokines
Weights and Measures
Control Groups
Therapeutics
Growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Intravesical interleukin-15 gene therapy in an orthotopic bladder cancer model. / Matsumoto, Kazuhiro; Kikuchi, Eiji; Horinaga, Minoru; Takeda, Toshikazu; Miyajima, Akira; Nakagawa, Ken; Oya, Mototsugu.

In: Human Gene Therapy, Vol. 22, No. 11, 01.11.2011, p. 1423-1432.

Research output: Contribution to journalArticle

Matsumoto, Kazuhiro ; Kikuchi, Eiji ; Horinaga, Minoru ; Takeda, Toshikazu ; Miyajima, Akira ; Nakagawa, Ken ; Oya, Mototsugu. / Intravesical interleukin-15 gene therapy in an orthotopic bladder cancer model. In: Human Gene Therapy. 2011 ; Vol. 22, No. 11. pp. 1423-1432.
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