TY - JOUR
T1 - Antibody-neutralized reovirus is effective in oncolytic virotherapy
AU - Berkeley, Robert A.
AU - Steele, Lynette P.
AU - Mulder, Aat A.
AU - Van Den Wollenberg, Diana J.M.
AU - Kottke, Timothy J.
AU - Thompson, Jill
AU - Coffey, Matthew
AU - Hoeben, Rob C.
AU - Vile, Richard G.
AU - Melcher, Alan
AU - Ilett, Elizabeth J.
N1 - Funding Information:
M. Coffey is chief executive officer at and has ownership interest in Oncolytics Biotech Inc. R.C. Hoeben reports receiving a commercial research grant from Crucell. A. Melcher reports receiving a commercial research grant from Oncolytics Biotech Inc. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This work was supported by a University of Leeds PhD scholarship award (to R.A. Berkeley). Publication costs were covered by Oncolytics Biotech. We thank Nik Matthews, Ritika Chauhan, and James Campbell for assistance with transcriptomic profiling and analysis.
Publisher Copyright:
© 2018 AACR.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
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U2 - 10.1158/2326-6066.CIR-18-0309
DO - 10.1158/2326-6066.CIR-18-0309
M3 - Article
C2 - 30209061
AN - SCOPUS:85054387874
SN - 2326-6066
VL - 6
SP - 1161
EP - 1173
JO - Cancer immunology research
JF - Cancer immunology research
IS - 10
ER -