Antibody-neutralized reovirus is effective in oncolytic virotherapy

Robert A. Berkeley, Lynette P. Steele, Aat A. Mulder, Diana J.M. Van Den Wollenberg, Timothy J. Kottke, Jill Thompson, Matthew Coffey, Rob C. Hoeben, Richard G. Vile, Alan Melcher, Elizabeth J. Ilett

Research output: Contribution to journalArticle

15 Scopus citations

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 FcgRIII) 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

Original languageEnglish (US)
Pages (from-to)1161-1173
Number of pages13
JournalCancer Immunology Research
Volume6
Issue number10
DOIs
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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    Berkeley, R. A., Steele, L. P., Mulder, A. A., Van Den Wollenberg, D. J. M., Kottke, T. J., Thompson, J., Coffey, M., Hoeben, R. C., Vile, R. G., Melcher, A., & Ilett, E. J. (2018). Antibody-neutralized reovirus is effective in oncolytic virotherapy. Cancer Immunology Research, 6(10), 1161-1173. https://doi.org/10.1158/2326-6066.CIR-18-0309