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Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity

Authors Hotta Y, Kasuya H, Bustos I, Naoe Y, Ichinose T, Tanaka M, Kodera Y

Received 9 November 2016

Accepted for publication 12 January 2017

Published 13 March 2017 Volume 2017:6 Pages 31—38

DOI https://doi.org/10.2147/OV.S127179

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Yoshihiro Hotta,1 Hideki Kasuya,2 Itzel Bustos,2 Yoshinori Naoe,2 Toru Ichinose,2 Maki Tanaka,3 Yasuhiro Kodera1

1Department of Surgery II, 2Cancer Immune Therapy Research Center, Nagoya University Graduate School of Medicine, Nagoya, 3Takara Bio Inc., Otsu, Japan


Background: HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. Importantly, it has also been noted that in mice with antitumors implanted on both sides of the back, an injection of HF10 on only one side strongly restrains not only the injected antitumor but also the non-injected ones.
Materials and methods: MC26 colon cancer cells were injected subcutaneously into the back, spleen, and intraperitoneal region of metastasis model mice. Antitumor volume and survival rate were monitored. To measure cytotoxic T lymphocytes (CTL) cytotoxicity against MC26, lymphocytes were extracted from the spleens of the peritoneal metastasis model mice as well as from the thymus of the liver metastasis model mice. The expression of interferon gamma was examined by enzyme-linked immunospot assay. Samples from the liver metastasis model mice were subjected to polymerase chain reaction to quantify the level of HSV genomes.
Results: HF10 was injected only on the back antitumor; however, a antitumor-suppressor effect was observed against liver and peritoneal metastases. When HF10 genome was measured, we observed lower genome on liver metastases compared to back antitumor genome quantity. CTL activity against MC26 was also observed. These results indicate that local administration of HF10 exerts a curative effect on systemic disease, mediated by host antitumor immunity.
Conclusion: HF10 local administration stimulates antitumor immunity to recognize antitumor-specific antigen, which then improves systemic disease. Metastatic antitumors lysis, on the other hand, appears to be mediated by the host immune system, rather than by virus-mediated direct oncolysis.

Keywords: herpes oncolytic virus, antitumor metastasis, immune response, T-cell-mediated cytotoxicity

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