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溶瘤腺病毒 XVir-N-31 作为一种新型疗法用于肌层浸润性膀胱癌。

The Oncolytic Adenovirus XVir-N-31 as a Novel Therapy in Muscle-Invasive Bladder Cancer.

机构信息

1 Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

2 Department of Radiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

出版信息

Hum Gene Ther. 2019 Jan;30(1):44-56. doi: 10.1089/hum.2018.026. Epub 2018 Aug 3.

Abstract

Muscle-invasive bladder cancer represents approximately 25% of diagnosed bladder cancer cases and carries a significant risk of death. Oncolytic viruses are novel antitumor agents with the ability to selectively replicate and lyse tumor cells while sparing healthy tissue. We explored the efficiency of the oncolytic YB-1-selective adenovirus XVir-N-31 in vitro and in an orthotopic mouse model for bladder cancer by intramural injection under ultrasound guidance. We demonstrated that XVir-N-31 replicated in bladder cancer cells and induced a stronger immunogenic cell death than wild-type adenovirus by facilitating enhanced release of HMGB1 and exosomal Hsp70. The intratumoral delivery of XVir-N-31 by ultrasound guidance delayed tumor growth in an immunodeficient model, demonstrating the feasibility of this approach to deliver oncolytic viruses directly into the tumor.

摘要

肌层浸润性膀胱癌约占膀胱癌诊断病例的 25%,具有较高的死亡风险。溶瘤病毒是一种新型抗肿瘤药物,能够选择性地复制和裂解肿瘤细胞,同时保护健康组织。我们通过超声引导下腔内注射,在体外和膀胱癌原位模型中探索了溶瘤 YB-1 选择性腺病毒 XVir-N-31 的效率。我们证明,XVir-N-31 在膀胱癌细胞中复制,并通过促进 HMGB1 和外泌体 HSP70 的释放,诱导比野生型腺病毒更强的免疫原性细胞死亡。超声引导下肿瘤内注射 XVir-N-31 可延迟免疫缺陷模型中的肿瘤生长,证明了这种直接将溶瘤病毒递送到肿瘤中的方法的可行性。

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