Targeted Photodynamic Virotherapy Armed with a Genetically Encoded Photosensitizer
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- Kiyoto Takehara
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Hiroshi Tazawa
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Naohiro Okada
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Yuuri Hashimoto
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Satoru Kikuchi
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Shinji Kuroda
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Hiroyuki Kishimoto
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Yasuhiro Shirakawa
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Nobuhiro Narii
- 3Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
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- Hiroyuki Mizuguchi
- 3Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
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- Yasuo Urata
- 4Oncolys BioPharma, Inc., Tokyo, Japan.
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- Shunsuke Kagawa
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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- Toshiyoshi Fujiwara
- 1Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
抄録
<jats:title>Abstract</jats:title> <jats:p>Photodynamic therapy (PDT) is a minimally invasive antitumor therapy that eradicates tumor cells through a photosensitizer-mediated cytotoxic effect upon light irradiation. However, systemic administration of photosensitizer often makes it difficult to avoid a photosensitive adverse effect. The red fluorescent protein KillerRed generates reactive oxygen species (ROS) upon green light irradiation. Here, we show the therapeutic potential of a novel tumor-specific replicating photodynamic viral agent (TelomeKiller) constructed using the human telomerase reverse transcriptase (hTERT) promoter. We investigated the light-induced antitumor effect of TelomeKiller in several types of human cancer cell lines. Relative cell viability was investigated using an XTT assay. The in vivo antitumor effect was assessed using subcutaneous xenografted tumor and lymph node metastasis models. KillerRed accumulation resulted in ROS generation and apoptosis in light-irradiated cancer cells. Intratumoral injection of TelomeKiller efficiently delivered the KillerRed protein throughout the tumors and exhibited a long-lasting antitumor effect with repeated administration and light irradiation in mice. Moreover, intratumorally injected TelomeKiller could spread into the regional lymph node area and eliminate micrometastasis with limited-field laser irradiation. Our results suggest that KillerRed has great potential as a novel photosensitizer if delivered with a tumor-specific virus-mediated delivery system. TelomeKiller-based PDT is a promising antitumor strategy to efficiently eradicate tumor cells. Mol Cancer Ther; 15(1); 199–208. ©2015 AACR.</jats:p>
収録刊行物
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- Molecular Cancer Therapeutics
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Molecular Cancer Therapeutics 15 (1), 199-208, 2016-01-01
American Association for Cancer Research (AACR)
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詳細情報 詳細情報について
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- CRID
- 1360004236369896448
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- ISSN
- 15388514
- 15357163
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- データソース種別
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