Oncolytic viral therapy with a combination of HF10, a herpes simplex virus type 1 variant and granulocyte–macrophage colony‐stimulating factor for murine ovarian cancer. Issue 12 (2nd December 2013)

• Record Type: Journal Article
• Authors: Goshima, Fumi; Esaki, Shinichi; Luo, Chenhong; Kamakura, Maki; Kimura, Hiroshi; Nishiyama, Yukihiro
• Is Part Of: International journal of cancer. Volume 134:Issue 12(2014:Jun. 15)
• Page Start: 2865
• Page End: 2877
• Publication Date: 2013-12-02
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28631
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Ovarian cancer is the most frequent cause of gynecological cancer‐related mortality as a majority of patients are diagnosed at an advanced stage with intraperitoneal dissemination because of the absence of initial symptoms. Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) plays an important role in the maturation of specialized antigen‐presenting cells. In this study, we utilized a herpes simplex virus (HSV) amplicon expressing murine GM‐CSF combined with HF10 (mGM‐CSF amplicon), a highly attenuated HSV type 1 strain functioning as a helper virus to strengthen anti‐tumor immune response, for the treatment of ovarian cancer with intraperitoneal dissemination. A mouse ovarian cancer cell line, OV2944‐HM‐1 (HM‐1), was intraperitoneally injected, following which HF10 only or the mGM‐CSF amplicon was injected intraperitoneally three times. HF10 injection prolonged survival and decreased intraperitoneal dissemination, but to a lesser extent than the mGM‐CSF amplicon. Although HF10 replication was not observed in HM‐1 cells, expression of VP5, a late gene coding the major capsid protein of HSV, was detected. Moreover, mGM‐CSF production was detected in transfected HM‐1 cells. Immunohistochemical staining revealed the infiltration of CD4‐ and CD8‐positive cells into the peritoneal tumor(s). A significantly increased CD4<sup>+</sup> T cell concentration was observed in the spleen. Murine splenic cells after each treatment were stimulated with HM‐1 cells, and the strongest immune response was observed in the mice that received mGM‐CSF amplicon injections. These results suggested that the mGM‐CSF amplicon is a promising agent for the treatment of advanced ovarian cancer with intraperitoneal dissemination.</p> </abstract>