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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 |
