Oncolytic activity of reovirus in HPV positive and negative head and neck squamous cell carcinoma

Journal of Otolaryngology-Head & Neck Surgery

Hadi Seikaly⁵  Maya Shmulevitz³  Thomas Carey²  Raymond Tam¹  David Fast⁴  Vincent L Biron⁵  Timothy Cooper⁵ 

[1] Faculty of Medicine and Dentistry, University of Alberta, 2J2 WC Mackenzie Health Sciences Centre, Edmonton T6G 2R7, AB, Canada;Department of Head and Neck Surgery, University of Michigan, 5311B Med Sci I, Ann Arbor 48109-5616, MI, USA;Department of Medical Microbiology and Immunology, University of Alberta, 6–142 J Katz Group Centre for Pharmacy & Health Research, Edmonton T6G 2E1, AB, Canada;Faculty of Science 1–001 CCIS, University of Alberta, Edmonton T6G 2E9, AB, Canada;Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Alberta, 1E4 University of Alberta Hospital, 1E4 Walter Mackenzie Center, 8440 112 St., Edmonton T6G 2B7, AB, Canada

关键词: HPV;    Squamous cell carcinoma;    Head and neck cancer;    Reovirus;   

Others  :  1132917
DOI  :  10.1186/s40463-015-0062-x

 received in 2014-08-05, accepted in 2015-02-09,  发布年份 2015

【 摘 要 】

Background

The management of patients with advanced stages of head and neck cancer requires a multidisciplinary and multimodality treatment approach which includes a combination of surgery, radiation, and chemotherapy. These toxic treatment protocols have significantly improved survival outcomes in a distinct population of human papillomavirus (HPV) associated oropharyngeal cancer. HPV negative head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat because there is only a modest improvement in survival with the present treatment regimens, requiring innovative and new treatment approaches. Oncolytic viruses used as low toxicity adjunct cancer therapies are novel, potentially effective treatments for HNSCC. One such oncolytic virus is Respiratory Orphan Enteric virus or reovirus. Susceptibility of HNSCC cells towards reovirus infection and reovirus-induced cell death has been previously demonstrated but has not been compared in HPV positive and negative HNSCC cell lines.

Objectives

To compare the infectivity and oncolytic activity of reovirus in HPV positive and negative HNSCC cell lines.

Methods

Seven HNSCC cell lines were infected with serial dilutions of reovirus. Two cell lines (UM-SCC-47 and UM-SCC-104) were positive for type 16 HPV. Infectivity was measured using a cell-based ELISA assay 18 h after infection. Oncolytic activity was determined using an alamar blue viability assay 96 h after infection. Non-linear regression models were used to calculate the amounts of virus required to infect and to cause cell death in 50% of a given cell line (EC₅₀). EC₅₀ values were compared.

Results

HPV negative cells were more susceptible to viral infection and oncolysis compared to HPV positive cell lines. EC₅₀ for infectivity at 18 h ranged from multiplicity of infection (MOI) values (PFU/cell) of 18.6 (SCC-9) to 3133 (UM-SCC 104). EC₅₀ for cell death at 96 h ranged from a MOI (PFU/cell) of 1.02×10² (UM-SCC-14A) to 3.19×10⁸ (UM-SCC-47). There was a 3×10⁶ fold difference between the least susceptible cell line (UM-SCC-47) and the most susceptible line (UM-SCC 14A) EC₅₀ for cell death at 96 h.

Conclusions

HPV negative HNSCC cell lines appear to demonstrate greater reovirus infectivity and virus-mediated oncolysis compared to HPV positive HNSCC. Reovirus shows promise as a novel therapy in HNSCC, and may be of particular benefit in HPV negative patients.

【 授权许可】

   
2015 Cooper et al.; licensee BioMed Central.

【 图 表 】

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