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.