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ADCC 增强:单克隆抗体治疗的难题还是福音?

ADCC enhancement: A conundrum or a boon to mAb therapy?

机构信息

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, 400019, India.

Department of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai, 400019, India.

出版信息

Biologicals. 2022 Sep;79:10-18. doi: 10.1016/j.biologicals.2022.08.006.

Abstract

The ability of antibodies to distinctly identify the antigens is an important feature exploited by the scientific community for the treatment of various diseases. The therapeutic action of monoclonal antibodies (mAbs) is mediated along with the cells of the immune system, such as natural killer cells, T cells and macrophages. The two major mechanisms that govern the therapeutic efficacy of mAbs are the antibody dependent cell mediated cytotoxicity (ADCC) and the complement dependent cytotoxicity (CDC). Consequently, much of the research dedicated to improving their action is focussed on enhancing either of these mechanisms. This manuscript focuses on the strategies to enhance ADCC, for providing more efficacious mAb therapeutics. These approaches essentially bring about changes in the elements of ADCC mechanism, such as the effector cell or the antibody itself and thus favour an enhanced therapeutic response. Several technologies of ADCC enhancement have been developed, based on the success of various strategies advanced by the researchers. These technologies show success with a few antibody therapeutics while they do not work with others. This review presents a detailed overview on these strategies and presents perspectives regarding the same.

摘要

抗体区分识别抗原的能力是科学界用于治疗各种疾病的重要特征。单克隆抗体(mAbs)的治疗作用是通过免疫系统的细胞介导的,如自然杀伤细胞、T 细胞和巨噬细胞。控制 mAbs 治疗效果的两个主要机制是抗体依赖的细胞介导的细胞毒性(ADCC)和补体依赖的细胞毒性(CDC)。因此,大部分致力于提高其作用的研究都集中在增强这两种机制上。本文重点介绍了增强 ADCC 的策略,以提供更有效的 mAb 治疗方法。这些方法主要通过改变 ADCC 机制的要素,如效应细胞或抗体本身,从而促进增强的治疗反应。已经开发了几种 ADCC 增强技术,这些技术基于研究人员提出的各种策略的成功。这些技术在一些抗体治疗药物中取得了成功,而在其他药物中则不起作用。本文对这些策略进行了详细的综述,并对其进行了展望。

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