Oncolytic activity of HF10 in head and neck squamous cell carcinomas

Abstract

Recent developments in therapeutic strategies have improved the prognosis of head and neck squamous cell carcinoma (HNSCC). Nevertheless, 5-year survival rate remains only 40%, necessitating new therapeutic agents. Oncolytic virotherapy entails use of replication-competent viruses to selectively kill cancer cells. We aimed to explore the potential of HF10 as an oncolytic virus against human or mouse HNSCC cell lines, and primary-cultured HNSCC cells. HF10 replicated well in all the HNSCC cells, in which it induced cytopathic effects and cell killing. Next, we investigated the oncolytic effects of HF10 in ear tumor models with human or mouse tumor cells. We detected HF10-infected cells within the ear tumors based on their expression of green fluorescent protein. HF10 injection suppressed ear tumor growth and prolonged overall survival. In the syngeneic model, HF10 infection induced tumor necrosis with infiltration of CD8-positive cells. Moreover, the splenocytes of HF10-treated mice released antitumor cytokines, IL-2, IL-12, IFN-alpha, IFN-beta, IFN-gamma, and TNF-alpha, after stimulation with tumor cells in vitro. The HF10-treated mice that survived their original tumor burdens rejected tumor cells upon re-challenge. These results suggested that HF10 killed HNSCC cells and induced antitumoral immunity, thereby establishing it as a promising agent for the treatment of HNSCC patients.

Oncolytic activity of naturally attenuated herpes-simplex virus HF10 against an immunocompetent model of oral carcinoma

“… 26 We have demonstrated the potential of HF10 as an oncolytic virus against head and neck, colorectal, ovarian, and breast cancers as well as melanoma in various mouse models. 6 , 7 , 8 , 24 In this study, HF10 was able to kill cancer cells isolated from either human or mouse tongue tumor. HF10 also decreased the volume of tongue tumors in vivo and prolonged mouse survival without causing weight loss or any side effects.…”

“…SCC-VII cells, derived from the murine abdominal wall, are the only cell lines available for studying squamous cell carcinoma. 23 Therefore, most murine oral cancer in vivo studies use SCC-VII cells for tumor establishment, 24 , 25 which may not be representative of oral carcinoma. Another murine model of oral cancer was generated by the addition of the carcinogen 4-NQO into drinking water.…”

“… 30 In this study, CD8-positive T cells were detected in tongue tumors following HF10 treatment, while CD4-positive T cells were not, both of which were in accordance with our previous studies. 5 , 24 We could not conduct a flowcytometric analysis since the tongue tumors were too small to remove from normal tongues. Instead, we counted CD8-positive cells using immunohistochemistry.…”

Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer

“…The SCC VII squamous cell carcinoma cell line is derived from the abdominal cavity of C3H mice [50][51][52], but widely used as a model for squamous cell carcinomas of head and neck cancer as it behaves similarly to human HNSCC [28,29,35,53]. In this study, we compared the efficacy of the TMV vaccine immunotherapy in SCC VII with recently available MOC models [7,31,33,37].…”

The Effect of Herpes Simplex Virus-Type-1 (HSV-1) Oncolytic Immunotherapy on the Tumor Microenvironment

“…The functions of these altered genes and how they may contribute to the antitumor efficacy of HF10 have been reviewed [ 57 ]. In a C3H mouse model of head and neck squamous cell carcinoma (SCC VII), intratumoral injection of HF10 reduced tumor growth and significantly enhanced survival [ 58 ]. Immunohistochemistry analysis showed evidence of tumor necrosis and infiltration of CD8+ T cells around HSV-infected cells in HF10 treated tumors [ 58 ].…”