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 Geoffrey Vile, Alan Melcher, Elizabeth J. Ilett

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 1 2018

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Oncolytic Virotherapy
Oncolytic Viruses
Antibodies
Neutralizing Antibodies
Antiviral Agents
Monocytes
Neoplasms
Cytotoxins
Immunotherapy
Immune System
Therapeutics
Infection

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Berkeley, R. A., Steele, L. P., Mulder, A. A., Van Den Wollenberg, D. J. M., Kottke, T. J., Thompson, J., ... 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

Antibody-neutralized reovirus is effective in oncolytic virotherapy. / Berkeley, Robert A.; Steele, Lynette P.; Mulder, Aat A.; Van Den Wollenberg, Diana J.M.; Kottke, Timothy J.; Thompson, Jill; Coffey, Matthew; Hoeben, Rob C.; Vile, Richard Geoffrey; Melcher, Alan; Ilett, Elizabeth J.

In: Cancer immunology research, Vol. 6, No. 10, 01.10.2018, p. 1161-1173.

Research output: Contribution to journalArticle

Berkeley, RA, Steele, LP, Mulder, AA, Van Den Wollenberg, DJM, Kottke, TJ, Thompson, J, Coffey, M, Hoeben, RC, Vile, RG, Melcher, A & Ilett, EJ 2018, 'Antibody-neutralized reovirus is effective in oncolytic virotherapy', Cancer immunology research, vol. 6, no. 10, pp. 1161-1173. https://doi.org/10.1158/2326-6066.CIR-18-0309
Berkeley RA, Steele LP, Mulder AA, Van Den Wollenberg DJM, Kottke TJ, Thompson J et al. Antibody-neutralized reovirus is effective in oncolytic virotherapy. Cancer immunology research. 2018 Oct 1;6(10):1161-1173. https://doi.org/10.1158/2326-6066.CIR-18-0309
Berkeley, Robert A. ; Steele, Lynette P. ; Mulder, Aat A. ; Van Den Wollenberg, Diana J.M. ; Kottke, Timothy J. ; Thompson, Jill ; Coffey, Matthew ; Hoeben, Rob C. ; Vile, Richard Geoffrey ; Melcher, Alan ; Ilett, Elizabeth J. / Antibody-neutralized reovirus is effective in oncolytic virotherapy. In: Cancer immunology research. 2018 ; Vol. 6, No. 10. pp. 1161-1173.
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