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

Autor: Xu C; Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany.; Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China., Goß AV; Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany., Dorneburg C; Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany., Debatin KM; Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany., Wei J; Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China., Beltinger C; Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany.
Jazyk: angličtina
Zdroj: Oncolytic virotherapy [Oncolytic Virother] 2018 Apr 30; Vol. 7, pp. 37-41. Date of Electronic Publication: 2018 Apr 30 (Print Publication: 2018).
DOI: 10.2147/OV.S150637
Abstrakt: 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 (TCID 50 ) 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.
Competing Interests: Disclosure The authors report no conflicts of interest in this work.
Databáze: MEDLINE
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