生物技术药物的免疫原性产生机制与控制策略

doi:10.19586/j.2095-2341.2024.0175

生物技术进展 ›› 2025, Vol. 15 ›› Issue (2): 212-219.DOI: 10.19586/j.2095-2341.2024.0175

生物技术药物的免疫原性产生机制与控制策略

崔兆惠(), 郭玲, 沈旭东, 林毅, 翟丽丽()

华北制药集团新药研究开发有限责任公司，抗体药物研制国家重点实验室，抗体药物河北省工程研究中心，石家庄 052160

收稿日期:2024-11-08 接受日期:2025-02-12 出版日期:2025-03-25 发布日期:2025-04-29
通讯作者: 翟丽丽
作者简介:崔兆惠 E-mail: zhaohuicui@126.com；
基金资助:
河北省重点研发计划项目(22372404D);石家庄市2022年生物医药研发奖补资金

Immunogenicity Formation Mechanism and Control Strategy of Biopharmaceuticals

Zhaohui CUI(), Ling GUO, Xudong SHEN, Yi LIN, Lili ZHAI()

Hebei Engineering Research Center of Antibody Medicine，State Key Laboratory of Antibody Research & Development，North China Pharmaceutical Group Corporation New Drug Research and Development Co. ，Ltd. ，Shijiazhuang 052160，China

Received:2024-11-08 Accepted:2025-02-12 Online:2025-03-25 Published:2025-04-29
Contact: Lili ZHAI

摘要/Abstract

摘要：

生物技术药物在肿瘤、自身免疫性疾病及其他复杂疾病的治疗中取得了日益显著的治疗效果。使用生物技术药物进行治疗时存在免疫原性风险，导致药物疗效和治疗效果降低，甚至产生严重的不良反应。在保持生物技术药物药代动力学特性和治疗效果的基础上，降低或去除其免疫原性成为药物开发过程的重要环节。了解驱动生物技术药物免疫原性的复杂机制以及制定有效的策略降低免疫原性风险对于提高药物疗效和安全性至关重要。综述了生物技术药物免疫原性产生机制的研究进展，讨论了影响免疫原性的因素，重点阐述了在药物开发过程中降低免疫原性的策略，以期为生物技术药物的研发提供参考。

关键词: 生物技术药物, 免疫原性, 抗药物抗体, 化学修饰, 聚集

Abstract:

Biopharmaceuticals have achieved increasingly significant therapeutic effects in the treatment of tumors， autoimmune diseases and other complex diseases. However， there is a risk of immunogenicity when using biopharmaceuticals for treatment， which can reduce drug efficacy and affect treatment outcomes， even cause severe adverse reactions. Reducing or eliminating the immunogenicity of biopharmaceuticals on the basis of maintaining their pharmacokinetic properties and therapeutic efficacy has become an important aspect of the drug development process. Understanding the complex mechanisms driving the immunogenicity of biopharmaceuticals and developing effective strategies to reduce immunogenicity risks are crucial for improving drug efficacy and safety. The article reviewed the development of mechanism of immunogenicity in biopharmaceuticals， discussed the factors that affected immunogenicity and focused on strategies used to reduce immunogenicity in drug development， in order to provide a reference for the research and development of biopharmaceuticals.

Key words: biopharmaceuticals, immunogenicity, anti?drug antibody, chemical modification, aggregation

中图分类号:

Q939.91

崔兆惠, 郭玲, 沈旭东, 林毅, 翟丽丽. 生物技术药物的免疫原性产生机制与控制策略[J]. 生物技术进展, 2025, 15(2): 212-219.

Zhaohui CUI, Ling GUO, Xudong SHEN, Yi LIN, Lili ZHAI. Immunogenicity Formation Mechanism and Control Strategy of Biopharmaceuticals[J]. Current Biotechnology, 2025, 15(2): 212-219.

图/表 2

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药物因素	患者因素
天然蛋白与治疗性蛋白的分子结构、氨基酸序列差异（人源化程度）	疾病类型（免疫介导/非免疫介导的疾病）
治疗性蛋白聚集	年龄
治疗性蛋白修饰-氧化、脱酰胺、糖基化	与其他药物同用
杂质、制剂组分、佐剂	剂量
剂型	治疗频率
生产过程	给药途径

药物因素	患者因素
天然蛋白与治疗性蛋白的分子结构、氨基酸序列差异（人源化程度）	疾病类型（免疫介导/非免疫介导的疾病）
治疗性蛋白聚集	年龄
治疗性蛋白修饰-氧化、脱酰胺、糖基化	与其他药物同用
杂质、制剂组分、佐剂	剂量
剂型	治疗频率
生产过程	给药途径

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生物技术药物的免疫原性产生机制与控制策略

Immunogenicity Formation Mechanism and Control Strategy of Biopharmaceuticals

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