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非人类灵长类动物衍生的腺病毒作为溶瘤剂的未来应用？

Non-Human Primate-Derived Adenoviruses for Future Use as Oncolytic Agents?

机构信息

Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.

出版信息

Int J Mol Sci. 2020 Jul 8;21(14):4821. doi: 10.3390/ijms21144821.

DOI:10.3390/ijms21144821
PMID:32650405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7404033/
Abstract

Non-human primate (NHP)-derived adenoviruses have formed a valuable alternative for the use of human adenoviruses in vaccine development and gene therapy strategies by virtue of the low seroprevalence of neutralizing immunity in the human population. The more recent use of several human adenoviruses as oncolytic agents has exhibited excellent safety profiles and firm evidence of clinical efficacy. This proffers the question whether NHP-derived adenoviruses could also be employed for viral oncolysis in human patients. While vaccine vectors are conventionally made as replication-defective vectors, in oncolytic applications replication-competent viruses are used. The data on NHP-derived adenoviral vectors obtained from vaccination studies can only partially support the suitability of NHP-derived adenoviruses for use in oncolytic virus therapy. In addition, the use of NHP-derived adenoviruses in humans might be received warily given the recent zoonotic infections with influenza viruses and coronaviruses. In this review, we discuss the similarities and differences between human- and NHP-derived adenoviruses in view of their use as oncolytic agents. These include their genome organization, receptor use, replication and cell lysis, modulation of the host's immune responses, as well as their pathogenicity in humans. Together, the data should facilitate a rational and data-supported decision on the suitability of NHP-derived adenoviruses for prospective use in oncolytic virus therapy.

摘要

非人灵长类动物（NHP）衍生的腺病毒由于人类群体中中和免疫的低血清流行率，已经成为疫苗开发和基因治疗策略中使用人腺病毒的有价值替代品。最近，几种人腺病毒被用作溶瘤剂，表现出了极好的安全性和坚实的临床疗效证据。这就提出了一个问题，即 NHP 衍生的腺病毒是否也可用于人类患者的病毒溶瘤治疗。虽然疫苗载体通常被制成复制缺陷型载体，但在溶瘤应用中使用复制型病毒。从疫苗接种研究中获得的关于 NHP 衍生腺病毒载体的数据只能部分支持 NHP 衍生腺病毒在溶瘤病毒治疗中的适用性。此外，鉴于最近发生的流感病毒和冠状病毒人畜共患感染，使用 NHP 衍生的腺病毒在人类中可能会引起警惕。在这篇综述中，我们讨论了人类和 NHP 衍生的腺病毒在用作溶瘤剂方面的相似性和差异。这些包括它们的基因组组织、受体使用、复制和细胞裂解、宿主免疫反应的调节以及它们在人类中的致病性。综上所述，这些数据应该有助于在合理的数据支持下，就 NHP 衍生腺病毒在溶瘤病毒治疗中的潜在用途做出决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/616ed8015da2/ijms-21-04821-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/4894d7998618/ijms-21-04821-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/7d08d16be39a/ijms-21-04821-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/616ed8015da2/ijms-21-04821-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/4894d7998618/ijms-21-04821-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/7d08d16be39a/ijms-21-04821-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c3/7404033/616ed8015da2/ijms-21-04821-g003.jpg

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