2011年11月
Intravesical Interleukin-15 Gene Therapy in an Orthotopic Bladder Cancer Model
HUMAN GENE THERAPY
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- 巻
- 22
- 号
- 11
- 開始ページ
- 1423
- 終了ページ
- 1432
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1089/hum.2011.013
- 出版者・発行元
- MARY ANN LIEBERT, INC
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 x 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 (5 mu g) 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 +/- 36 mg, 201 +/- 35 mg, and 96 +/- 29 mg, 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.
- リンク情報
- ID情報
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- DOI : 10.1089/hum.2011.013
- ISSN : 1043-0342
- eISSN : 1557-7422
- PubMed ID : 21554107
- Web of Science ID : WOS:000297373100013