title: Reovirus-mediated cytotoxicity and enhancement of innate immune responses against acute myeloid leukemia.
abstract: Reovirus is a naturally occurring oncolytic virus that has shown preclinical efficacy in the treatment of a wide range of tumor types and has now reached phase III testing in clinical trials. The anti-cancer activity of reovirus has been attributed to both its direct oncolytic activity and the enhancement of anti-tumor immune responses. In this study, we have investigated the direct effect of reovirus on acute myeloid leukemia (AML) cells and its potential to enhance innate immune responses against AML, including the testing of primary samples from patients. Reovirus was found to replicate in and kill AML cell lines, and to reduce cell viability in primary AML samples. The pro-inflammatory cytokine interferon alpha (IFNα) and the chemokine (C-C motif) ligand 5 (known as RANTES [regulated upon activation, normal T-cell expressed, and secreted]) were also secreted from AML cells in response to virus treatment. In addition, reovirus-mediated activation of natural killer (NK) cells, within the context of peripheral blood mononuclear cells, stimulated their anti-leukemia response, with increased NK degranulation and IFNγ production and enhanced killing of AML targets. These data suggest that reovirus has the potential as both a direct cytotoxic and an immunotherapeutic agent for the treatment of AML.
authors.affiliation: Leeds Institute of Molecular Medicine, St. James's University Hospital , Leeds, United Kingdom .
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hall
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Scott
authors.forename: Ailsa
authors.initials: A
authors.lastname: Rose
authors.forename: Michael
authors.initials: M
authors.lastname: Desborough
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
authors.forename: Christopher
authors.initials: C
authors.lastname: Parrish
authors.forename: Richard
authors.initials: R
authors.lastname: Vile
authors.forename: Matt
authors.initials: M
authors.lastname: Coffey
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.forename: Fiona
authors.initials: F
authors.lastname: Errington-Mais
authors.forename: Alan A
authors.initials: AA
authors.lastname: Melcher
keywords: NK cells; acute myeloid leukemia; immunotherapy; oncolytic virus; reovirus