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免疫系统——腺病毒疗法的双刃剑。

The Immune System-A Double-Edged Sword for Adenovirus-Based Therapies.

机构信息

Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

Systems Immunity University Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

出版信息

Viruses. 2024 Jun 17;16(6):973. doi: 10.3390/v16060973.

DOI:10.3390/v16060973
PMID:38932265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11209478/
Abstract

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

摘要

致病性腺病毒（Ad）感染广泛存在，但通常为轻度和短暂的，除非在免疫功能低下的情况下。作为基因治疗、疫苗和肿瘤学应用的载体，基于腺病毒的平台具有优势，包括易于基因操作、大规模生产和成熟的安全性概况，使其成为治疗开发的有吸引力的工具。然而，免疫系统通常构成了一个重大挑战，必须克服这个挑战，才能使基于腺病毒的治疗真正有效。人群中预先存在的抗腺病毒免疫力以及针对工程化腺病毒载体的免疫反应的快速发展，都会对基于腺病毒的治疗的下游影响产生不利影响。本综述重点讨论了在先天和适应性免疫反应的背景下，基于腺病毒的治疗所面临的不同挑战，包括预先存在的自然免疫力和由治疗引起的抗载体免疫力。我们总结了旨在解决这些问题的不同方法及其结果和潜在的未来应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/609d64b2d28f/viruses-16-00973-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/e5945f83519a/viruses-16-00973-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/3ae98e2bfdaf/viruses-16-00973-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/cb5e2326464e/viruses-16-00973-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/0b4601eb4248/viruses-16-00973-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/77c1341fc9ff/viruses-16-00973-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/609d64b2d28f/viruses-16-00973-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/e5945f83519a/viruses-16-00973-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/3ae98e2bfdaf/viruses-16-00973-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/cb5e2326464e/viruses-16-00973-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/0b4601eb4248/viruses-16-00973-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/77c1341fc9ff/viruses-16-00973-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f7/11209478/609d64b2d28f/viruses-16-00973-g006.jpg

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