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

Kathryn Hall, Karen J. Scott, Ailsa Rose, Michael Desborough, Kevin Harrington, Hardev Pandha, Christopher Parrish, Richard Vile, Matt Coffey, David Bowen, Fiona Errington-Mais, Alan A. Melcher

Research output: Contribution to journalArticle

13 Scopus citations

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 IFNc 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.

Original languageEnglish (US)
Pages (from-to)3-15
Number of pages13
JournalBioResearch Open Access
Volume1
Issue number1
DOIs
StatePublished - 2012

Keywords

  • Acute myeloid leukemia
  • Immunotherapy
  • NK cells
  • Oncolytic virus
  • Reovirus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hall, K., Scott, K. J., Rose, A., Desborough, M., Harrington, K., Pandha, H., Parrish, C., Vile, R., Coffey, M., Bowen, D., Errington-Mais, F., & Melcher, A. A. (2012). Reovirus-mediated cytotoxicity and enhancement of innate immune responses against acute myeloid leukemia. BioResearch Open Access, 1(1), 3-15. https://doi.org/10.1089/biores.2012.0205