慢性乙型肝炎的免疫治疗

吴晓敏; 仝巧云; 刘伟

doi:10.3969/j.issn.1001-5256.2019.11.040

慢性乙型肝炎的免疫治疗

DOI: 10.3969/j.issn.1001-5256.2019.11.040

三峡大学第一临床医学院

基金项目:

国家自然科学基金项目(31600134)；

详细信息

中图分类号: R512.62
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出版历程
- 收稿日期: 2019-07-01
- 出版日期: 2019-11-20

Immunotherapy for chronic hepatitis B

Department of Gastroenterology,The First Clinical Medical College of China Three Gorges University

Research funding:

摘要

摘要: 虽然目前直接抗HBV药物在控制病毒复制和限制肝硬化进展方面非常有效,但慢性乙型肝炎的治疗仍任重而道远。免疫耐受及免疫功能失调可能是最重要的免疫致病因素。针对抗HBV免疫治疗的新策略及正在研发的新药不断兴起,综合国际最新研究成果,主要阐述近年来慢性乙型肝炎免疫治疗的研究进展。
- 乙型肝炎,慢性 /
- 免疫疗法,主动 /
- 免疫法,被动
Abstract: Although current direct anti-hepatitis B virus( HBV) drugs have good effects in controlling viral replication and limiting the progression to liver cirrhosis,there is still a long way to go in the treatment of chronic hepatitis B( CHB). Immune tolerance and immune dysfunction may be the two most important immunopathogenic factors. With reference to the development of new strategies and new drugs for anti-HBV immunotherapy and the latest research findings around the world,this article reviews the research advances in immunotherapy for CHB in recent years.
- hepatitis B,chronic /
- immunotherapy,active /
- immunization,passive

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参考文献(37)

[1] WHO. Hepatitis B fact sheets[EB/OL].(2019-07-19)[2019-07-01]. Http://www. who. Int/news-room/fact-sheets/detail/hepatitis-b.

[2] Polaris Observatory Collaborators. Global prevalence,treatment,and prevention of hepatitis B virus infection in 2016:A modellingstudy[J]. Lancet Gastroenterol Hepatol,2018,3(6):383-403.

[3] ZHAO H. The epidemiology of hepatitis B virus infection in China[J]. J Viral Hepat,2018,25(12):1624.

[4] YUE MF,CHEN DS,GEOFFREY M,et al. Hepatitis B virus infection[J]. Nat Rev Dis Primers,2018,4:18036.

[5] JIANG FM,CHENG SQ. Expression and clinical significance of Toll-like receptors 3 and 4 in patients with chronic hepatitis B[J]. Int J Virol,2017,24(3):209-212.(in Chinese)蒋福明，程书权．慢性乙型肝炎患者Toll样受体3、4的表达及其临床意义[J]．国际病毒学杂志，2017,24(3):209-212.

[6] PEERIDOGAHEH H,MESHKAT Z,HABIBZADEH S,et al. Current concepts on immunopathogenesis of hepatitis B virus infection[J]. Virus Res,2018,245:29-43.

[7] TSENG TC,HUANG LR. Immunopathogenesis of hepatitis B virus[J]. J Infect Dis,2017,216(S8):s765-s770.

[8] ZHAO YM,GAO MD,SUN JP,et al. Research progress of depleted CD8+T cells[J]. Int J Virol,2019,26(2):139-142.(in Chinese)赵亚楠，高梦丹，孙坚萍，等．耗竭型CD8+T细胞的研究进展[J]．国际病毒学杂志，2019,26(2):139-142.

[9] BERTOLETTI A,le BERT N. Immunotherapy for chronic hepatitis B virus infection[J]. Gut Liver,2018,12(5):497-507.

[10] WALSH R,HAMMOND R,JACKSON K,et al. Effects of SB9200(Inarigivir)therapy on immune responses in patients with chronic hepatitis B[J]. J Hepatol,2018,68(S1):s89.

[11] YUEN M,CHEN C,LIU C,et al. Ascending dose cohort study of inarigivir-a novel RIG I agonist in chronic HBV patients:Final results of the ACHIEVE trial[J]. J Hepatol,2019,70(S1):e47-e48.

[12] COLLEDGE D,JACKSON K,SOZZI V,et al. The novel antiviral agent inarigivir inhibits both nucleos(t)ide analogue and capsid assembly inhibitor resistant HBV in vitro[J]. J Hepatol,2019,70(S1):e476-e477.

[13] NIU C,LI L,DAFFIS S,et al. Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism[J]. J Hepatol,2018,68(5):922-931.

[14] AGARWAL K,AHN SH,ELKHASHAB M,et al. Safety and efficacy of vesatolimod(GS-9620)in patients with chronic hepatitis B who are not currently on antiviral treatment[J]. J Viral Hepat,2018,25(11):1331-1340.

[15] HERSCHKE F,LI C,de CREUS A,et al. Antiviral activity of JNJ-4964(AL-034/TQ-A3334),a selective toll-like receptor 7 agonist,in AAV/HBV mice after oral administration for12 weeks[J]. J Hepatol,2019,70(S1):e49-e50.

[16] DAFFIS S,CHAMBERLAIN J,ZHENG J,et al. Sustained efficacy and surface antigen seroconversion in the woodchuck model of chronic hepatitis B with the selective tolllike receptor 8agonist GS-9688[J]. J Hepatol,2017,66(1):s692-s693.

[17] AMIN OE,COLBECK E,DAFFIS S,et al. In vitro modulation by TLR8 agonist GS-9688 of multiple regulatory cell types in patients with chronic hepatitis B[J]. J Hepatol,2019,70(S1):e445-e446.

[18] TIO M,RAI R,EZEOKE OM,et al. Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant,HIV or hepatitis B/C infection[J]. Eur J Cancer,2018,104:137-144.

[19] ZHANG F,WEI H,WANG X,et al. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade[J]. Cell Discov,2017,3:17004.

[20] ALI R,SINGH S,HAQ W. IAP proteins antagonist:an introduction and chemistry of smac mimetics under clinical development[J]. Curr Med Chem,2018,25(31):3768-3795.

[21] PAN W,LUO Q,YAN X,et al. A novel SMAC mimetic APG-1387 exhibits dual antitumor effect on HBV-positive hepatocellular carcinoma with high expression of cIAP2 by inducing apoptosis and enhancing innate anti-tumor immunity[J]. Biochem Pharmacol,2018,154:127-135.

[22] KAH J,KOH S,VOLZ T,et al. Lymphocytes transiently expressing virus-specific T cell receptors reducehepatitis B virus infection[J]. J Clin Invest,2017,127(8):3177-3188.

[23] KRUSE RL,SHUM T,TASHIRO H,et al. HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liverchimeric mice[J]. Cytotherapy,2018,20(5):697-705.

[24] WISSKIRCHEN K,METZGER K,SCHREIBER S,et al. Isolation and functional characterization of hepatitis B virus-specific T-cellreceptors as new tools for experimental and clinical use[J]. PLo S One,2017,12(8):e0182936.

[25] LUCIFORA J,XIA Y,REISINGER F,et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA[J]. Science,2014,343(6176):1221-1228.

[26] MEIER MA,SUSLOV A,KETTERER S,et al. Hepatitis B virus covalently closed circular DNA homeostasis is independent of the lymphotoxin pathway during chronic HBV infection[J]. J Viral Hepat,2017,24(8):662-671.

[27] MARTIN P,DUBOIS C,JACQUIER E,et al. TG1050,an immunotherapeutic to treat chronic hepatitis B,induces robust T cells and exerts an antiviral effect in HBV-persistent mice[J]. Gut,2015,64(12):1961-1971.

[28] KRATZER R,SANSAS B,LLU K,et al. A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model[J]. Hum Vaccin Immunother,2018,14(6):1417-1422.

[29] PAULSEN D,WEBER O,RUEBSAMEN SH. AIC649 induces a bi-phasic treatment response in the woodchuck model of chronic hepatitis B[J]. PLo S One,2015,10(12):e0144383.

[30] ADDY I,JAMBRECINA A,BERG T,et al. First in human,single ascending dose clinical trial of AIC649 in patients with chronic hepatitis[J]. J Hepatol,2019,70(S1):e478-e479.

[31] Inovio’s news and media. Inovio’s DNA immunotherapy demonstrates immune response results key in treating chronic hepatitis B infection[EB/OL].(2018-03-04)[2019-07-01].http://ir. inovio. com/news-and-media/news/press-release-details/2018/Inovios-DNA-Immunotherapy-Demonstrates-Immune-Response-Results-Key-in-Treating-Chronic-Hepatitis-B-Infection.

[32] TANG L,CHEN C,GAO X,et al. Interleukin 21 reinvigorates the antiviral activity of hepatitis B virus(HBV)-specific CD8+T cells in chronic HBV infection[J]. J Infect Dis,2019,219(5):750-759.

[33] WANG X,XU ZQ,FU JJ,et al. Role of interleukin-21 and interleukin-21 receptor polymorphisms in the treatment of HBe Ag-positive chronic hepatitis B patients with peginterferon[J]. Medicine(Baltimore),2018,97(23):e10891.

[34] SHEN Z,YANG H,YANG S,et al. Hepatitis B virus persistence in mice reveals IL-21 and IL-33 as regulators of viral clearance[J]. Nat Commun,2017,8(1):2119.

[35] ZENG Z,KONG X,LI F,et al. IL-12-based vaccination therapy reverses liver-induced systemic tolerance in a mouse model of hepatitis B virus carrier[J]. J Immunol,2013,191(8):4184-4193.

[36] RIGOPOULOU EI,SURI D,CHOKSHI S,et al. Lamivudine plus interleukin-12 combinationtherapy in chronic hepatitis B:Antiviral and immunological activity[J]. Hepatology,2005,42(5):1028-1036.

[37] SCHIRDEWAHN T,GRABOWSKI J,OWUSU SEKYERE S,et al. The third signal cytokine interleukin 12 rather than immune checkpoint inhibitors contributes to the functional restoration of hepatitis D virus-specific T cells[J]. J Infect Dis,2017,215(1):139-149.

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