Chun Xu, Annika Verena Goß, Carmen Dorneburg, Klaus-Michael Debatin, Jiwu Wei, Christian Beltinger
{"title":"Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies.","authors":"Chun Xu, Annika Verena Goß, Carmen Dorneburg, Klaus-Michael Debatin, Jiwu Wei, Christian Beltinger","doi":"10.2147/OV.S150637","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (TCID<sub>50</sub>) 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19491,"journal":{"name":"Oncolytic Virotherapy","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2018-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OV.S150637","citationCount":"6","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncolytic Virotherapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/OV.S150637","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 6
Abstract
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.