Oncolytic activity of HF10 in head and neck squamous cell carcinomas.
Shinichi EsakiFumi GoshimaHaruka OzakiGaku TakanoYoshimi HatanoDaisuke KawakitaKei IjichiTakahiro WatanabeYoshitaka SatoTakayuki MurataHiromitsu IwataYuta ShibamotoShingo MurakamiYukihiro NishiyamaHiroshi KimuraPublished in: Cancer gene therapy (2019)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- acute heart failure
- endothelial cells
- immune response
- endoplasmic reticulum stress
- end stage renal disease
- high glucose
- stem cells
- cell death
- rheumatoid arthritis
- oxidative stress
- chronic kidney disease
- type diabetes
- mass spectrometry
- diabetic rats
- drug induced
- peritoneal dialysis
- atrial fibrillation
- climate change
- prognostic factors
- squamous cell
- ejection fraction
- free survival
- replacement therapy
- disease virus