1. ¹Department of Virology, Graduate School of Medicine, Nagoya University, Nagoya, Japan
2. ²Research Division, M's Science Corporation, Kobe, Japan
3. ³Department of Obstetrics and Genecology, Graduate School of Medicine, Nagoya University, Nagoya, Japan
4. ⁴Department of Otorhinolaryngology, Graduate School of Medicine, Nagoya University, Nagoya, Japan
5. ⁵Department of Dermatology, Aichi Medical University, Aichi, Japan
6. ⁶Division of Virology, Aichi Cancer Center Research Institute, Nagoya, Japan

Correspondence: Professor Y Nishiyama, Department of Virology, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: ynishiya@med.nagoya-u.ac.jp

Received 15 September 2006; Revised 5 April 2007; Accepted 19 April 2007; Published online 10 August 2007.

Abstract

Direct viral infection of solid tumors can cause tumor cell death, but these techniques offer the opportunity to express exogenous factors to enhance the antitumor response. We investigated the antitumor effects of a herpes simplex virus (HSV) amplicon expressing mouse granulocyte–macrophage colony-stimulating factor (mGM-CSF) using the replication-competent HSV type 1 mutant HF10 as a helper virus. HF10-packaged mGM-CSF-expressing amplicon (mGM-CSF amplicon) was used to infect subcutaneously inoculated murine colorectal tumor cells (CT26 cells) and the antitumor effects were compared to tumors treated with only HF10. The mGM-CSF amplicon efficiently replicated in CT26 cells with similar oncolytic activity to HF10 in vitro. However, when mice subcutaneously inoculated with CT26 cells were intratumorally injected with HF10 or mGM-CSF amplicon, greater tumor regression was seen in mGM-CSF amplicon-treated animals. Furthermore, mGM-CSF amplicon treatment prolonged mouse survival. Immunohistochemical analysis revealed increased inflammatory cell infiltration in the solid tumor in the mGM-CSF amplicon-treated animals. These results suggest that expression of GM-CSF enhances the antitumor effects of HF10, and HF10-packaged GM-CSF-expressing amplicon is a promising agent for the treatment of subcutaneous tumors.