Targeted delivery of interferon‐α to hepatitis B virus‐infected cells usin

StephenW

Targeted delivery of interferon‐α to hepatitis B virus‐infected cells using T cell receptor‐like antibodies

    Changhua Ji1,†,*,
    Konduru SR Sastry2,
    Georg Tiefenthaler3,
    Jennifer Cano1,
    Tenny Tang1,
    ZI Zong Ho2,
    Denise Teoh2,
    Sandhya Bohini1,
    Antony Chen2,
    Surya Sankuratri1,
    Paul A Macary4,
    Patrick Kennedy5,
    Han Ma1,
    Stefan Ries3,
    Klaus Klumpp1,
    Erhard Kopetzki3,
    Antonio Bertoletti2,6,7,‡,*

DOI: 10.1002/hep.25875

During antiviral therapy, specific delivery of interferon‐α (IFNα) to infected cells may increase its antiviral efficacy, trigger a localized immune reaction and reduce the side effects caused by systemic administration. Two T‐cell receptor‐like antibodies (TCR‐L) able to selectively bind Hepatitis B virus (HBV) infected hepatocytes of chronic hepatitis B patients and recognize core (HBc18‐27) and surface (HBs183‐91) HBV epitopes associated with different Human Leucocytes Antigen (HLA)‐A*2 alleles (A*2:1, A*2:2, A*2:7, A*2:11) were generated. Each antibody was genetically linked to two IFNα molecules to produce TCR‐L/IFNα fusion proteins. We demonstrated that the fusion proteins triggered an IFNα response preferentially on the hepatocytes presenting the correct HBV‐peptide HLA‐complex and that the mechanism of the targeted IFNα response was dependent on the specific binding of the fusion proteins to the HLA/HBV peptide complexes through the TCR‐like variable regions of the antibodies. TCR‐L antibodies can be used to target cytokines to HBV infected hepatocytes in vitro. Fusion of IFNα to TCR‐L decreased the intrinsic biological activity of IFNα but preserved the overall specificity of the protein for the cognate HBV peptide/HLA complexes. This induction of an effective IFNα response selectively in HBV infected cells might have a therapeutic advantage in comparison to the currently used native or pegylated IFNα. (HEPATOLOGY 212.)

StephenW

α-干扰素，乙肝病毒感染的细胞，T细胞受体抗体针对性的交付

    彰化Ji1，†*
    konduru简Sastry2，
    格奥尔格Tiefenthaler3
    詹妮弗Cano1
    tenny Tang1
    訾宗HO2，
    丹尼斯Teoh2
    sandhya Bohini1
    安东尼陈，
    苏里亚Sankuratri1
    保罗Macary4，
    帕特里克Kennedy5
    韩MA1，
    斯特凡Ries3
    克劳斯Klumpp1
    艾哈德Kopetzki3
    安东尼奥Bertoletti2，6,7，‡*

DOI：10.1002/hep.25875

α-干扰素（IFNα的）具体交付给受感染的细胞的抗病毒治疗期间，可能会增加其抗病毒疗效，引发局部的免疫反应，减少副作用引起全身给药的影响。与不同的两个T细胞受体抗体（TCR -  L）能选择性地结合慢性乙型肝炎患者的乙型肝炎病毒（HBV）感染的肝细胞，并承认核心（HBc18-27）和表面（HBs183-91）乙肝病毒抗原表位人类白细胞抗原（HLA）*2等位基因（*2:1*2:2*2:7*2:11）产生。每个抗体基因与两个α干扰素分子，生产TCR-L/IFNα的融合蛋白。我们表明，融合蛋白优先目标IFNα的反应机制是依赖于具体的融合蛋白结合的HLA/ HBV肽复合物，通过提出正确的HBV-肽HLA复杂的肝细胞和IFNα的反应引发T细胞受体抗体的可变区一样。 TCR-L的抗体可用于目标乙肝病毒感染的肝细胞在体外的细胞因子。 TCR-L的融合干扰素α下降IFNα的内在的生物活性，但保留了整体同源HBV肽/ HLA复合物特异性蛋白。这可能有一个有效的IFNα的反应在HBV感染的细胞选择性诱导在比较目前使用的原生或聚乙二醇干扰素α治疗的优势。 （肝病212）。

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希望 有比聚乙二醇干扰素更好的干扰素出现