Oncolytic virotherapy for head and neck cancer: current research and future developments

Oncolytic Virotherapy, Jul 2015

Oncolytic virotherapy for head and neck cancer: current research and future developments Akshiv Malhotra,1 Arun Sendilnathan,1 Matthew O Old,2 Trisha M Wise-Draper11Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, 2Department of Otolaryngology-Head and Neck Surgery, Ohio State University, Columbus, OH, USAAbstract: Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Despite recent advancements in surgical, chemotherapy, and radiation treatments, HNC remains a highly morbid and fatal disease. Unlike many other cancers, local control rather than systemic control is important for HNC survival. Therefore, novel local therapy in addition to systemic therapy is urgently needed. Oncolytic virotherapy holds promise in this regard as viruses can be injected intratumorally as well as intravenously with excellent safety profiles. This review will discuss the recent advancements in oncolytic virotherapy, highlighting some of the most promising candidates and modifications to date.Keywords: head and neck cancer, virotherapy, oncolytic viruses

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Oncolytic virotherapy for head and neck cancer: current research and future developments

Authors Malhotra A, Sendilnathan A, Old M, Wise-Draper T Received 26 March 2015 Accepted for publication 12 May 2015 Published 20 July 2015 Volume 2015:4 Pages 83—93 DOI https://doi.org/10.2147/OV.S54503 Checked for plagiarism Yes Review by Single-blind Peer reviewer comments 4 Editor who approved publication: Dr Faris Farassati Akshiv Malhotra,1 Arun Sendilnathan,1 Matthew O Old,2 Trisha M Wise-Draper1 1Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, 2Department of Otolaryngology-Head and Neck Surgery, Ohio State University, Columbus, OH, USA Abstract: Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Despite recent advancements in surgical, chemotherapy, and radiation treatments, HNC remains a highly morbid and fatal disease. Unlike many other cancers, local control rather than systemic control is important for HNC survival. Therefore, novel local therapy in addition to systemic therapy is urgently needed. Oncolytic virotherapy holds promise in this regard as viruses can be injected intratumorally as well as intravenously with excellent safety profiles. This review will discuss the recent advancements in oncolytic virotherapy, highlighting some of the most promising candidates and modifications to date. Keywords: head and neck cancer, virotherapy, oncolytic viruses Introduction Head and neck cancer (HNC) remains a global health concern accounting for 650,000 new cases each year, resulting in 350,000 deaths worldwide. The identification of human papillomavirus (HPV) infection as a favorable prognostic factor has fueled clinical studies investigating deintensification strategies in this HPV-positive disease subset. However, the overall survival of HPV-negative tumors remains poor despite intensive therapy. Early stage localized tumors are often cured with a single modality, including surgical resection or radiation therapy; however, locally advanced HNC often requires multimodality treatment. Despite primary intensive treatment of locally advanced disease, relapse rates at 2 years remain at 30%–50%,1–3 resulting in 5-year survival of less than 10% in the relapsed and metastatic group.4 Even though the addition of targeted agents, such as the epidermal growth factor receptor (EGFR) inhibitor, cetuximab, has resulted in incremental rise in overall survival both in locally advanced and metastatic disease, the overall impact has been minimal.4,5 Novel therapeutic strategies are desperately required to further advance the success in HNC treatment. Several exciting areas of investigation are ongoing, including other molecular-targeted therapy, immunotherapy, gene therapy, as well as oncolytic virotherapy, as means of improving treatment outcomes and reducing morbidity in HNC treatment. Here, we review the background, feasibility, and potential role for oncolytic virotherapy in the treatment in HNC. Oncolytic virotherapy Oncolytic virotherapy is a promising approach as a cancer therapeutic, especially in its potential for local tumor control and low morbidity. Oncolytic viruses have the ability to selectively replicate in tumor cells via deletion of critical virulence genes that are required for replication in the normal host. Several oncolytic viruses have been tested both preclinically and in clinical trials (Tables 1 and 2), demonstrating safety and, in some instances, activity in human tumors. HNC allows for a unique opportunity for the application of these viruses as locoregional control is often most critical in this disease. Here, we will review the most common oncolytic viruses and their potential use as therapy in HNC. Table 1 Summary of oncolytic viruses in clinical studies Abbreviations: HSV, herpes simplex virus; VSV, vesicular stomatitis virus; GM-CSF, granulocyte-macrophage colony-stimulating factor; UL, long unique region; RUC-GFP, Renilla luciferase-Aequorea green fluorescent protein; 5-FU, 5-flurouracil; HNC, head and neck cancer; SCC, squamous cell carcinoma; HNSCC, head and neck squamous cell carcinoma. Table 2 Summary of oncolytic viruses in preclinical studies Abbreviations: HSV, herpes simplex virus; VSV, vesicular stomatitis virus; NDV, Newcastle disease virus; 5-FC, 5-fluorocytosine; 5-FU, 5-flurouracil; CD/UPRT, cytosine deaminase/uracil phosphoribosyltransferase; HNSCC, head and neck squamous cell carcinoma; HNC, head and neck cancer; EGFR, epidermal growth factor receptor. Oncolytic adenovirus One of the first engineered replication selective viruses to be tested in humans in clinical trials are the adenoviruses. The adenoviruses are naturally cytolytic, nonenveloped, double-stranded DNA viruses. Oncolytic adenoviruses contain modifications conferring tumor-selective replication. Modifications include deletion of the p300/CBP-binding or the pRB-binding region of E1A (resulting in selective killing of tumor cells with defect (...truncated)


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Akshiv Malhotra, Arun Sendilnathan, Matthew O Old, Trisha M Wise-Draper. Oncolytic virotherapy for head and neck cancer: current research and future developments, Oncolytic Virotherapy, 2015, pp. 83-93, DOI: 10.2147/OV.S54503