Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies
Authors Xu C, Goß AV, Dorneburg C, Debatin KM, Wei J, Beltinger C
Received 1 September 2017
Accepted for publication 26 January 2018
Published 30 April 2018 Volume 2018:7 Pages 37—41
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Faris Farassati
Chun Xu,1,2,* Annika Verena Goß,1,* Carmen Dorneburg,1 Klaus-Michael Debatin,1 Jiwu Wei,2 Christian Beltinger1
1Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany; 2Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China
*These authors contributed equally to this work
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: acute lymphoblastic leukemia, oncolytic measles virus, anti-measles antibodies, decoy for anti-measles antibodies
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