通过桥接感染细胞和免疫效应细胞的双特异性 T 细胞接合抗体激活适应性免疫,是治疗慢性乙型肝炎的一种有前景的新型疗法。
Activating adaptive immunity by bispecific, T-cell engager antibodies bridging infected and immune-effector cells is a promising novel therapy for chronic hepatitis B.
发表日期:2024 Sep
作者:
Zhe Xie, Ulrike Protzer
来源:
ANTIVIRAL RESEARCH
摘要:
双特异性抗体 (bsAb) 是一种工程免疫球蛋白,在一个分子中结合了两个不同的抗原结合位点。 BsAb 可分为两种分子形式:IgG 样抗体和非 IgG 样抗体。每种形式的结构元素对免疫系统的参与都有影响。 T 细胞接合抗体 (TCE) 是设计用于使 T 细胞与靶细胞接合的双特异性抗体。 TCE 不仅可以应用于癌症,还可以应用于传染病治疗,以激活 T 细胞反应。在这篇综述中,我们重点关注有关双特异性抗体的设计和使用的最新文献,作为增强适应性抗病毒免疫反应的创新策略。我们总结了以 TCE 为重点的新型 T 细胞相关免疫疗法,这些疗法是为治疗慢性乙型肝炎而开发的。 2022 年,慢性乙型肝炎病毒 (HBV) 感染导致 110 万人死亡,主要原因是超过 2.5 亿慢性感染者罹患肝硬化和肝细胞癌。慢性乙型肝炎缺乏治疗方法。将抗病毒疗法与激活T细胞反应的免疫疗法相结合被认为是治愈乙型肝炎和预防慢性感染后遗症的最有前途的治疗方法。吸引非 HBV 特异性且因此尚未暴露于调节机制的功能完整的 T 细胞并激活肝脏靶位点的 T 细胞是一种非常有趣的治疗方法,可以通过 TCE 实现。因此,将 T 细胞重定向至 HBV 阳性细胞的 TCE 代表了治疗慢性乙型肝炎和 HBV 相关肝细胞癌的一种有前景的策略。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。
Bispecific antibodies (bsAbs) are engineered immunoglobulins that combine two different antigen-binding sites in one molecule. BsAbs can be divided into two molecular formats: IgG-like and non-IgG-like antibodies. Structural elements of each format have implications for engaging the immune system. T cell engager antibodies (TCEs) are bsAbs designed to engage T cells with target cells. TCEs can be applied not only in cancer but also in infectious disease therapy to activate T-cell responses. In this review, we focus on current literature on the design and use of bsAbs as an innovative strategy to enhance adaptive antiviral immune responses. We summarized the novel T cell-related immunotherapies with a focus on TCEs, that are developed for the treatment of chronic hepatitis B. Chronic infection with the hepatitis B virus (HBV) had a death toll of 1.1 million humans in 2022, mainly due to liver cirrhosis and hepatocellular carcinoma developing in the more than 250 million humans chronically infected. A curative treatment approach for chronic hepatitis B is lacking. Combining antiviral therapy with immune therapies activating T-cell responses is regarded as the most promising therapeutic approach to curing HBV and preventing the sequelae of chronic infection. Attracting functionally intact T cells that are not HBV-specific and, therefore, have not yet been exposed to regulatory mechanisms and activating those at the target site in the liver is a very interesting therapeutic approach that could be achieved by TCEs. Thus, TCEs redirecting T cells toward HBV-positive cells represent a promising strategy for treating chronic hepatitis B and HBV-associated hepatocellular carcinoma.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.