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

IF 6.7
Oncolytic Virotherapy Pub Date : 2018-04-30 eCollection Date: 2018-01-01 DOI:10.2147/OV.S150637
Chun Xu, Annika Verena Goß, Carmen Dorneburg, Klaus-Michael Debatin, Jiwu Wei, Christian Beltinger
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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.

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诱骗病毒保护溶瘤性麻疹病毒免受中和抗体的原理证明。
背景:麻疹减毒病毒(OMV)在早期临床试验中是一种很有前景的抗肿瘤药物。然而,预先存在的麻疹免疫可能是OMV治疗的障碍。方法:采用短波紫外光灭活OMV。用Vero细胞进行组织培养感染剂量50 (TCID50)测定,用Jurkat细胞进行流式细胞术测定,证实了uv灭活的OMV具有复制丧失和溶瘤活性。酶联免疫吸附试验验证了紫外线灭活的OMV仍然具有抗原性。在添加麻疹免疫血清的培养基中预培养不同剂量的uv灭活OMV。将混合物转移到Jurkat细胞中,加入活性OMV。流式细胞术检测omv诱导的Jurkat细胞活性死亡。结果:紫外线灭活可抑制OMV的复制,同时保持其抗原性。紫外线灭活的OMV在Jurkat细胞培养中隔离预先存在的抗mv抗体,从而保护活性的OMV不被中和并保持溶瘤活性。结论:我们证明了不复制的OMV可以作为中和抗mv抗体的“诱饵”,从而使OMV具有抗肿瘤活性的原理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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