Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy.
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Date
2018-10-01ICR Author
Author
Berkeley, RA
Steele, LP
Mulder, AA
van den Wollenberg, DJM
Kottke, TJ
Thompson, J
Coffey, M
Hoeben, RC
Vile, RG
Melcher, A
Ilett, EJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Monocytes
Cell Line
Animals
Mice, Inbred C57BL
Humans
Reoviridae
Melanoma, Experimental
Immunoglobulin A
Immunoglobulin G
Receptors, IgG
Antibodies, Viral
Female
Oncolytic Virotherapy
Oncolytic Viruses
Antibodies, Neutralizing
Chlorocebus aethiops
Research team
Translational Immunotherapy
Language
eng
Date accepted
2018-08-16
License start date
2018-10
Citation
Cancer immunology research, 2018, 6 (10), pp. 1161 - 1173
Publisher
AMER ASSOC CANCER RESEARCH