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刘爽, 孙钰芳, 邱熙然, 等. 抗体药物Fc段结构域改造研究进展[J]. 中国临床医学, 2024, 31(1): 143-153. DOI: 10.12025/j.issn.1008-6358.2024.20222225
引用本文: 刘爽, 孙钰芳, 邱熙然, 等. 抗体药物Fc段结构域改造研究进展[J]. 中国临床医学, 2024, 31(1): 143-153. DOI: 10.12025/j.issn.1008-6358.2024.20222225
LIU Shuang, SUN Yufang, QIU Xiran, et al. Research progress on structural domain modification of the Fc segment of antibody drugs[J]. Chinese Journal of Clinical Medicine, 2024, 31(1): 143-153. DOI: 10.12025/j.issn.1008-6358.2024.20222225
Citation: LIU Shuang, SUN Yufang, QIU Xiran, et al. Research progress on structural domain modification of the Fc segment of antibody drugs[J]. Chinese Journal of Clinical Medicine, 2024, 31(1): 143-153. DOI: 10.12025/j.issn.1008-6358.2024.20222225

抗体药物Fc段结构域改造研究进展

Research progress on structural domain modification of the Fc segment of antibody drugs

  • 摘要: 抗体是生物体内应对外来物质入侵时产生的主要保护物质,是保护生物体的重要分子。对抗体的Fc段进行改造可有效延长抗体的半衰期,大大减少给药剂量;Fc段介导的抗体效应子的功能也可以根据疾病特殊性进行上调或下调,实现治疗效果最大化。同时,仅有Fc片段的抗体,也可具备结合抗原的能力,通过缩小抗体分子的大小,可大大减少抗体分子量大的限制,为抗体药物的开发提供了新的方向。此外,除抗肿瘤作用外,抗体分子在抗感染领域也发挥了重要的作用。对抗感染中和抗体Fc区进行工程改造,可有效促进保护性的细胞免疫效应,增强抗病毒活性并延长半衰期。本文总结了抗体Fc结构域的功能特性及优化策略,并介绍Fc结构域优化改造所介导的生物学效应及在临床治疗中的应用与发展。

     

    Abstract: Antibodies are the main protective substance produced in the organism in response to the invasion of foreign substances, and are important molecules to protect the organism. By modifying the Fc segment of the antibody, the half-life of the antibody can be effectively extended, and the dosage can be reduced greatly; and the function of Fc-segment-mediated antibody effectors can also be up-regulated or down-regulated according to the specificity of the disease to maximize the therapeutic effect. Antibodies with only Fc fragments also have the ability to bind antigens. In order to reduce the size of antibody molecules and greatly reduce the limitation of antibody molecular weight, it provides a new direction for the development of antibody drugs. Furthermore, in addition to anti-tumor effects, antibody molecules also play an important role in the field of anti-infection. By engineering the Fc region of anti-infection neutralizing antibodies, it can effectively promote protective cellular immune effects, enhance anti-viral activity and prolong the half-life. This review summarizes the functional properties and optimization strategies of the Fc structural domain, and discusses the biological effects mediated by the optimal modification of the Fc structural domain and its application and development in clinical therapy.

     

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