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Cancer Immunol Res. 2018 Oct;6(10):1161-1173. doi: 10.1158/2326-6066.CIR-18-0309. Epub 2018 Sep 12.

Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy.

Author information

1
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
2
Leiden University Medical Centre, Department of Molecular Cell Biology, Leiden, the Netherlands.
3
Department of Immunology, Mayo Clinic, Rochester, Minnesota.
4
Oncolytics Biotech Incorporated, Calgary, Alberta, Canada.
5
Institute of Cancer Research, London, United Kingdom.
6
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom. e.ilett@leeds.ac.uk.

Abstract

Immunotherapy is showing promise for otherwise incurable cancers. Oncolytic viruses (OVs), developed as direct cytotoxic agents, mediate their antitumor effects via activation of the immune system. However, OVs also stimulate antiviral immune responses, including the induction of OV-neutralizing antibodies. Current dogma suggests that the presence of preexisting antiviral neutralizing antibodies in patients, or their development during viral therapy, is a barrier to systemic OV delivery, rendering repeat systemic treatments ineffective. However, we have found that human monocytes loaded with preformed reovirus-antibody complexes, in which the reovirus is fully neutralized, deliver functional replicative reovirus to tumor cells, resulting in tumor cell infection and lysis. This delivery mechanism is mediated, at least in part, by antibody receptors (in particular FcγRIII) that mediate uptake and internalization of the reovirus/antibody complexes by the monocytes. This finding has implications for oncolytic virotherapy and for the design of clinical OV treatment strategies. Cancer Immunol Res; 6(10); 1161-73. ©2018 AACR.

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