Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma

Alena C. Jaime-Ramirez, Jun Ge Yu, Enrico Caserta, Ji Young Yoo, Jianying Zhang, Tae Jin Lee, Craig Hofmeister, John H. Lee, Bhavna Kumar, Quintin Pan, Pawan Kumar, Robert Baiocchi, Theodoros Teknos, Flavia Pichiorri, Balveen Kaur, Matthew Old

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Oncolytic viruses (OVs) are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin), a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I–III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA) orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs), which have a 5-year survival of ∼55%. Histone deacetylase inhibitors (HDACis) comprise a structurally diverse class of compounds with targeted anti-cancer effects. The first FDA-approved HDACi, vorinostat (suberoylanilide hydroxamic acid [SAHA]), is currently being tested in patients with head and neck cancer. Recent findings indicate that HDAC inhibition in myeloma cells results in the upregulation of the Reolysin entry receptor, junctional adhesion molecule 1 (JAM-1), facilitating reovirus infection and tumor cell killing both in vitro and in vivo. In this study, we tested the anti-tumor efficacy of HDAC inhibitors AR-42 or SAHA in conjunction with Reolysin in HNSCCs. While HDAC inhibition increased JAM-1 and reovirus entry, the impact of this combination therapy was tested on the development of anti-tumor immune responses.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalMolecular Therapy Oncolytics
Volume5
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Keywords

  • head and neck cancer
  • immune impact
  • oncolytics
  • reovirus

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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