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。 |
关键词: 抗体 Fc结构域 效应子 分子改造 临床应用 |
DOI:10.12025/j.issn.1008-6358.2024.20222225 |
分类号: |
基金项目:国家重点研发计划(2021YFC2300400),国家自然基金面上项目(82173864). |
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Research progress on structural domain modification of the Fc segment of antibody drugs |
LIU Shuang1, SUN Yufang1, QIU Xiran1, AN Maomao1, SHEN Hui2
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1.Department of Pharmacy, Tenth People's Hospital, Tongji University, Shanghai 200072, China;2.Department of Laboratory Medicine, Tenth People's Hospital, Tongji University, Shanghai 200072, China
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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. |
Key words: antibody Fc domain effector molecular modification clinical applications |