RRC ID 43078
Author Kohno SI, Luo C, Nawa A, Fujimoto Y, Watanabe D, Goshima F, Tsurumi T, Nishiyama Y.
Title Oncolytic virotherapy with an HSV amplicon vector expressing granulocyte-macrophage colony-stimulating factor using the replication-competent HSV type 1 mutant HF10 as a helper virus.
Journal Cancer Gene Ther
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.
Volume 14(11)
Pages 918-26
Published 2007-11-1
DOI 10.1038/sj.cgt.7701070
PII 7701070
PMID 17693992
MeSH Animals Colorectal Neoplasms / pathology Colorectal Neoplasms / therapy* Genetic Therapy / methods* Genetic Vectors* Granulocyte-Macrophage Colony-Stimulating Factor / genetics* Helper Viruses / genetics* Herpesvirus 1, Human / genetics* Mice Mice, Inbred BALB C Oncolytic Virotherapy* Virus Replication Xenograft Model Antitumor Assays
IF 4.534
Times Cited 31
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY ONCOLOGY
Resource
Human and Animal Cells Vero(RCB0001) COS-7(RCB0539)