Abstract
Prognosis for advanced oral carcinoma remains poor. Oncolytic virotherapy uses replication-competent viruses to infect and kill only the tumor cells. However, it has been difficult to investigate the oncolytic activity of viruses against oral carcinomas in mouse models. This study established a mouse model of oral cancer and investigated the in vitro and in vivo anti-tumor effects of HF10, a highly attenuated, replication-competent herpes simplex virus (HSV)-1. Mouse tongue cancer was induced by injecting 4-nitroquinoline 1-oxide into the mouse tongue. The murine oral cancer cell line isolated from this tumor, named NMOC1, formed invasive carcinoma within a week when injected into mouse tongue. HF10 successfully infected, replicated, and spread in the cancer cells in vitro. HF10 was able to kill cancer cells isolated from human or mouse tongue tumor. HF10 injection into tongue carcinomas prolonged mouse survival without any side effects or weight loss. Intertumoral injection of GFP-expressing HF10 confirmed that viral spread was confined within the tumors. Immunohistochemical staining showed that HF10 induced infiltration of CD8-positive T cells around HSV-infected cells in the tumor mass, implying increased anti-tumor immunity. We successfully established an oral cancer cell line and showed that HF10 is a promising therapeutic agent for oral cancer.
Highlights
The use of viruses for cancer treatment has been reported as early as the 1950s.1 In 1974, a study in Japan that used the mumps virus for treating terminal cancer had positive results in 37 out of 90 patients;[2] further clinical studies were not performed
Previous murine models of oral cancer were generated by the addition of the carcinogen 4-nitroquinoline 1-oxide (4-NQO) to drinking water for 6 months.[20]
In this study, we aimed to establish a stable model of murine oral cancer
Summary
The use of viruses for cancer treatment has been reported as early as the 1950s.1 In 1974, a study in Japan that used the mumps virus for treating terminal cancer had positive results in 37 out of 90 patients;[2] further clinical studies were not performed. The use of viruses for cancer treatment has been reported as early as the 1950s.1. In 1974, a study in Japan that used the mumps virus for treating terminal cancer had positive results in 37 out of 90 patients;[2] further clinical studies were not performed. After a genetically attenuated virus displayed effectivity in treating a mouse model of glioma in 1991,3 more researchers focused on using attenuated viruses for cancer treatment in what is called “oncolytic virotherapy.”. We have previously shown the anti-tumor effects of HF10 in various tumor models.[5,6,7,8,9] Recently, several clinical trials have demonstrated the safety and efficacy of HF10.10
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