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Reovirus-mediated cytotoxicity and enhancement of innate immune responses against acute myeloid leukemia.

Hall, K, Scott, KJ, Rose, A, Desborough, M, Harrington, K, Pandha, H, Parrish, C, Vile, R, Coffey, M, Bowen, D , Errington-Mais, F and Melcher, AA (2012) Reovirus-mediated cytotoxicity and enhancement of innate immune responses against acute myeloid leukemia. Biores Open Access, 1 (1). pp. 3-15.

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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.

Item Type: Article
Authors :
NameEmailORCID
Hall, KUNSPECIFIEDUNSPECIFIED
Scott, KJUNSPECIFIEDUNSPECIFIED
Rose, AUNSPECIFIEDUNSPECIFIED
Desborough, MUNSPECIFIEDUNSPECIFIED
Harrington, KUNSPECIFIEDUNSPECIFIED
Pandha, Hh.pandha@surrey.ac.ukUNSPECIFIED
Parrish, CUNSPECIFIEDUNSPECIFIED
Vile, RUNSPECIFIEDUNSPECIFIED
Coffey, MUNSPECIFIEDUNSPECIFIED
Bowen, DUNSPECIFIEDUNSPECIFIED
Errington-Mais, FUNSPECIFIEDUNSPECIFIED
Melcher, AAUNSPECIFIEDUNSPECIFIED
Date : January 2012
Identification Number : 10.1089/biores.2012.0205
Uncontrolled Keywords : NK cells, acute myeloid leukemia, immunotherapy, oncolytic virus, reovirus
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:52
Last Modified : 17 May 2017 14:45
URI: http://epubs.surrey.ac.uk/id/eprint/825436

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