Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy.
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Embargo End Date
ICR Authors
Authors
Berkeley, RA
Steele, LP
Mulder, AA
van den Wollenberg, DJM
Kottke, TJ
Thompson, J
Coffey, M
Hoeben, RC
Vile, RG
Melcher, A
Ilett, EJ
Steele, LP
Mulder, AA
van den Wollenberg, DJM
Kottke, TJ
Thompson, J
Coffey, M
Hoeben, RC
Vile, RG
Melcher, A
Ilett, EJ
Document Type
Journal Article
Date
2018-10-01
Date Accepted
2018-08-16
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.
Citation
Cancer immunology research, 2018, 6 (10), pp. 1161 - 1173
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
2326-6066
eISSN
2326-6074
Collections
Research Team
Translational Immunotherapy