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肿瘤靶向性遮蔽抗体研究进展

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抗体药物作为肿瘤靶向治疗的重要手段之一,能够通过特异性结合肿瘤细胞表面抗原,精准杀伤肿瘤细胞,但因脱靶毒性等问题限制其在实体瘤治疗中的广泛应用。随着抗体工程技术的不断发展,新型肿瘤靶向性遮蔽抗体被开发,减少了抗体药物的脱靶不良反应。遮蔽抗体主要由抗体单元、遮蔽单元和连接子组成,具有在肿瘤组织中选择性激活等特点,目前已研发多种具有不同特点的遮蔽抗体技术。动物实验结果表明,遮蔽抗体均具有较好的药物安全性。本文对肿瘤靶向性遮蔽抗体的结构和特性、常见遮蔽抗体技术及其药物研发现状进行综述,以期为研发新型抗肿瘤靶向药物提供思路。
Research progress in tumor-targeted masked antibodies
Antibody-based therapies are one of the crucial tumor-targeted therapies,enabling pre-cise elimination of tumor cells by specifically binding to antigens on the tumor cell surface.However,their wide applications in solid tumor therapy are often limited by on-target toxicity.Recent advance-ments in antibody engineering have led to the development of novel tumor-targeted masking antibod-ies,which are specifically designed to address these limitations.Masking antibodies typically consist of an antibody domain,a masking domain and a linker.These antibodies are characterized by selective activation and other functional properties.Currently,various masking antibody technologies with distinct characteristics have been developed and have demonstrated favorable safety profiles in animal studies.This review summarizes the structure and characteristics of tumor-targeted masking antibodies outlines common masking technologies and their drug development in order to offer new lines of thought for the design and development of next-generation tumor-targeted therapeutics.

tumorstumor-targeted therapymasked antibodytumor microenvironmenttumor-associated protease

邹健平、姚新欣、温淳、朱珊、张世慧、张晓晶

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赣南医科大学赣南创新与转化医学研究院,重大疾病新药靶发现及新药创制全国重点实验室,江西 赣州 341000

肿瘤 靶向治疗 遮蔽抗体 肿瘤微环境 肿瘤相关蛋白酶

2025

中国药理学与毒理学杂志
军事医学科学院毒物药物研究所,中国药理学会,中国毒理学会

中国药理学与毒理学杂志

北大核心
影响因子:1.182
ISSN:1000-3002
年,卷(期):2025.39(1)