Abstract 706: A novel photodynamic therapy with virus-mediated delivery of photosensitive cytotoxic fluorescent protein KillerRed for human cancers

Abstract

Abstract Photodynamic therapy (PDT) is an antitumor strategy to induce tumor-specific cytotoxicity through accumulation of photosensitizers (PSs) and following light irradiation. Specific wavelength light irradiation induces the PS-mediated generation of reactive oxygen species (ROS) and subsequent cytotoxicity in tumor cells. Currently, some kinds of PSs, such as photofrin and laserphyrin, are used for PDT on clinical settings. However, the lack of sufficient and continuous accumulation of PSs in tumor tissues makes difficult to eradicate tumor cells by PDT. Therefore, the development of novel strategy for accumulation of PS in tumor tissues more efficiently and persistently is required to improve the antitumor effect of PDT. A bioengineered fluorescent protein KillerRed has been previously reported to generate ROS upon green light irradiation, suggesting a potential of KillerRed fluorescent protein as a novel PS. We recently confirmed that transient or stable transfection with KillerRed-expressing plasmid vector suppressed the cell viability through induction of ROS-mediated apoptosis in various types of human cancer cells when combined with light irradiation. In this study, we generated non-replicative adenovirus expressing KillerRed (Ad-KillerRed) and telomerase-specific conditionally replicating adenovirus expressing KillerRed (CRAd-KillerRed) to induce efficient accumulation of KillerRed in tumor cells. The in vitro antitumor effect of these viruses was investigated in human cancer H1299, HCT116 and HT29 cells in combination with light irradiation. Ad-KillerRed at high dose suppressed cell viability of human cancer cells when combined with light irradiation. In contrast, CRAd-KillerRed suppressed cell viability of human cancer cells more efficiently compared to Ad-KillerRed in combination with light irradiation. These results suggest that virus-mediated delivery system of KillerRed is a promising strategy for novel PDT. Now, in vivo experiments are under way to investigate antitumor effect of these viruses. Citation Format: Kiyoto Takehara, Hiroshi Tazawa, Yuuri Hashimoto, Hiroyuki Kishimoto, Toshiyoshi Fujiwara, Nobuhiro Narii, Hiroyuki Mizuguchi. A novel photodynamic therapy with virus-mediated delivery of photosensitive cytotoxic fluorescent protein KillerRed for human cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 706. doi:10.1158/1538-7445.AM2014-706