Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies

Oncolytic Virotherapy
Chun XuChristian Beltinger

Abstract

Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID50) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. We prove the principle that a non-replicating OMV can serve as a "decoy" for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV.

Citations

Mar 19, 2020·Oncolytic Virotherapy·Nadishka JayawardenaMihnea Bostina
Feb 5, 2021·Cancers·Christine E Engeland, Guy Ungerechts

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

Graph Pad Prism
FlowJo

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