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


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.


CONCLUSIONS
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.
Department of Surgery II.
Yoshihiro
Y
Hotta
Cancer Immune Therapy Research Center, Nagoya University Graduate School of Medicine, Nagoya.
Hideki
H
Kasuya
Cancer Immune Therapy Research Center, Nagoya University Graduate School of Medicine, Nagoya.
Itzel
I
Bustos
Cancer Immune Therapy Research Center, Nagoya University Graduate School of Medicine, Nagoya.
Yoshinori
Y
Naoe
Cancer Immune Therapy Research Center, Nagoya University Graduate School of Medicine, Nagoya.
Toru
T
Ichinose
Takara Bio Inc., Otsu, Japan.
Maki
M
Tanaka
Department of Surgery II.
Yasuhiro
Y
Kodera
T-cell-mediated cytotoxicity; antitumor metastasis; herpes oncolytic virus; immune response