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[用于治疗慢性乙型肝炎病毒感染的免疫疗法——以嵌合抗原受体T细胞为重点的概述]

[Immunotherapies for the treatment of chronic hepatitis B virus infections-an overview with a focus on CAR T cells].

作者信息

Ivics Zoltan, Amberger Maximilian, Zahn Tobias, Hildt Eberhard

机构信息

Abteilung Biotechnologie, Paul-Ehrlich-Institut, Langen, Deutschland.

Abteilung Virologie, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225, Langen, Deutschland.

出版信息

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2020 Nov;63(11):1357-1364. doi: 10.1007/s00103-020-03223-7. Epub 2020 Sep 29.

DOI:10.1007/s00103-020-03223-7
PMID:32995895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7647999/
Abstract

More than 250 million people worldwide suffer from chronic infection with hepatitis B virus (CHB). Chronic infection is associated with an increased risk of developing liver fibrosis/cirrhosis and hepatocellular carcinoma. Approximately 0.8-1 million people die annually as a result of CHB. One difficulty in the treatment of CHB is that the viral genome can persist for a very long time in the form of a minichromosome, and viral sequences can insert themselves into the host genome. Chronic infections are often characterized by functional defects of the cellular immune response, especially the T‑cell response, which prevents the elimination of HBV-infected cells.Immunotherapies aiming to cure CHB therefore aim to restore the antiviral function of the cellular immune response. In this review, various current approaches to immunotherapy of CHB are described, in particular the use of genetically modified autologous T cells as a possible tool for therapy. Furthermore, the modulation of checkpoint inhibitors of the immune response, metabolic T cell therapies, and therapeutic vaccination to stimulate the T‑cell response are summarized as immunotherapeutic strategies for treating CHB.

摘要

全球超过2.5亿人患有慢性乙型肝炎病毒(CHB)感染。慢性感染会增加发生肝纤维化/肝硬化和肝细胞癌的风险。每年约有80万至100万人死于CHB。CHB治疗的一个难点在于病毒基因组可以以微型染色体的形式长期存在,并且病毒序列可以插入宿主基因组。慢性感染通常以细胞免疫反应,特别是T细胞反应的功能缺陷为特征,这阻碍了对HBV感染细胞的清除。因此,旨在治愈CHB的免疫疗法旨在恢复细胞免疫反应的抗病毒功能。在这篇综述中,描述了目前治疗CHB的各种免疫疗法,特别是使用基因改造的自体T细胞作为一种可能的治疗工具。此外,免疫反应检查点抑制剂的调节、代谢性T细胞疗法以及刺激T细胞反应的治疗性疫苗接种被总结为治疗CHB的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/98205ee2af4a/103_2020_3223_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/170b44edb8f9/103_2020_3223_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/9fe1b4b18d15/103_2020_3223_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/98205ee2af4a/103_2020_3223_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/170b44edb8f9/103_2020_3223_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/9fe1b4b18d15/103_2020_3223_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb40/7647999/98205ee2af4a/103_2020_3223_Fig3_HTML.jpg

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本文引用的文献

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Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches.慢性乙型肝炎病毒感染中 T 细胞功能障碍的发病机制及相关治疗方法。
Front Immunol. 2020 May 12;11:849. doi: 10.3389/fimmu.2020.00849. eCollection 2020.
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Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential.乙型肝炎病毒共价闭合环状 DNA:形成、调控和治疗潜力。
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Targeting Host Innate and Adaptive Immunity to Achieve the Functional Cure of Chronic Hepatitis B.
靶向宿主固有免疫和适应性免疫以实现慢性乙型肝炎的功能性治愈
Vaccines (Basel). 2020 May 11;8(2):216. doi: 10.3390/vaccines8020216.
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Checkpoint Inhibitors and Therapeutic Vaccines for the Treatment of Chronic HBV Infection.检查点抑制剂和治疗性疫苗治疗慢性乙型肝炎病毒感染。
Front Immunol. 2020 Mar 4;11:401. doi: 10.3389/fimmu.2020.00401. eCollection 2020.
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Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection.靶向固有和适应性免疫系统以治愈慢性乙型肝炎病毒感染的研究进展。
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A new approach for therapeutic vaccination against chronic HBV infections.一种针对慢性乙型肝炎病毒感染的治疗性疫苗接种新方法。
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Adoptive T-cell therapy for HBV-associated HCC and HBV infection.用于乙肝相关肝癌和乙肝感染的过继性T细胞疗法。
Antiviral Res. 2020 Apr;176:104748. doi: 10.1016/j.antiviral.2020.104748. Epub 2020 Feb 19.
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The Regulation of HBV Transcription and Replication.HBV 转录和复制的调控。
Adv Exp Med Biol. 2020;1179:39-69. doi: 10.1007/978-981-13-9151-4_3.
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