Department of Urology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Department of Oral and Maxillofacial Surgery, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
Int J Mol Sci. 2021 Sep 29;22(19):10522. doi: 10.3390/ijms221910522.
Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors allow for genetic manipulations that restrict tumour specificity and also the expression of specific transgenes in order to support the anti-tumour effect. Additionally, replication of the virus and reinfection of neighbouring tumour cells amplify the therapeutic effect. Another important aspect in oncolytic adenovirus therapy is the virus induced cell death which is a process that activates the immune system against the tumour. This review describes which elements in adenovirus vectors have been identified for modification not only to utilize oncolytic adenovirus vectors into conditionally replicating adenoviruses (CRAds) that allow replication specifically in tumour cells but also to confer specific characteristics to these viruses. These advances in development resulted in clinical trials that are summarized based on the conceptual design.
溶瘤腺病毒治疗作为一种治疗各种癌症的新方法越来越受到重视。腺病毒载体内的不同修饰概念已被确定,这些概念定义了其对肿瘤的作用方式和相互作用。腺病毒载体允许进行基因操作,从而限制肿瘤的特异性,并在表达特定转基因时支持抗肿瘤效应。此外,病毒的复制和邻近肿瘤细胞的再感染会放大治疗效果。溶瘤腺病毒治疗的另一个重要方面是病毒诱导的细胞死亡,这是一个激活免疫系统对抗肿瘤的过程。本综述描述了腺病毒载体中的哪些元件已被确定用于修饰,不仅将溶瘤腺病毒载体利用为条件复制腺病毒(CRAds),使其能够在肿瘤细胞中特异性复制,而且还赋予这些病毒特定的特征。这些开发进展导致了临床试验的出现,本综述基于概念设计对这些临床试验进行了总结。