抗体药物筛选技术的研究进展

doi:10.19586/j.2095-2341.2024.0149

生物技术进展 ›› 2025, Vol. 15 ›› Issue (1): 43-49.DOI: 10.19586/j.2095-2341.2024.0149

抗体药物筛选技术的研究进展

纪思佳¹(), 张小雪¹, 翟丽丽¹, 董静¹, 李岩异², 常亮¹()

^1.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
^2.华北制药金坦生物技术股份有限公司，石家庄 050035

收稿日期:2024-09-14 接受日期:2024-10-14 出版日期:2025-01-25 发布日期:2025-03-07
通讯作者: 常亮
作者简介:纪思佳E-mail: hbjisijia@163.com；
基金资助:
河北省重点研发计划项目(22372401D)

Research Progress of Antibody Drug Screening Technology

Sijia JI¹(), Xiaoxue ZHANG¹, Lili ZHAI¹, Jing DONG¹, Yanyi LI², Liang CHANG¹()

^1.State Key Laboratory of Antibody Research & Development，Hebei Engineering Research Center of Antibody Medicine，North China Pharmaceutical Group Corporation New Drug Research and Development Co. ，Ltd. ，Shijiazhuang 052160，China
^2.NCPC Genetech Biotechnology Co. ，Ltd. ，Shijiazhuang 050035，China

Received:2024-09-14 Accepted:2024-10-14 Online:2025-01-25 Published:2025-03-07
Contact: Liang CHANG

摘要/Abstract

摘要：

抗体药物经历了多克隆抗体、单克隆抗体及基因工程抗体三个阶段，随着人类对抗体药物的不断深入研究，出现了多克隆抗体技术、杂交瘤抗体技术、抗体文库展示技术以及转基因小鼠技术等多种抗体筛选技术。抗体药物具有非常大的发展前景，针对各种抗体药物筛选技术的特点进行整理归纳，并讨论了抗体药物研发面临的挑战，以期为后续抗体技术的发展提供参考。

关键词: 抗体文库展示技术, 转基因小鼠技术, 单个B细胞抗体技术, 人工智能

Abstract:

Antibody drugs have gone through three stages： polyclonal antibody， monoclonal antibody and genetically engineered antibody. With the continuous deepening of human research on antibody drugs， a variety of antibody screening technologies have emerged， such as polyclonal antibody technology， hybridoma antibody technology， antibody library display technology and transgenic mouse technology. Antibody drugs have a very large development prospect. The article summarized the characteristics of various antibody drug screening technologies， and discussed the challenges faced by antibody drug research and development， in order to provide reference for the subsequent development of antibody technology.

Key words: antibody library display technology, transgenic mouse technology, single B cell antibody technique, artificial intelligence

中图分类号:

Q511

纪思佳, 张小雪, 翟丽丽, 董静, 李岩异, 常亮. 抗体药物筛选技术的研究进展[J]. 生物技术进展, 2025, 15(1): 43-49.

Sijia JI, Xiaoxue ZHANG, Lili ZHAI, Jing DONG, Yanyi LI, Liang CHANG. Research Progress of Antibody Drug Screening Technology[J]. Current Biotechnology, 2025, 15(1): 43-49.

图/表 5

图1 抗体文库展示技术示意图（以噬菌体为例）[17]

Fig. 1 Antibody library display technology diagram (phage as an example)[17]

图2 转基因小鼠技术筛选人源化抗体示意图[24]

Fig. 2 Schematic diagram of transgenic mouse technology screening for humanized antibodies[24]

图3 基于单个B细胞抗体技术筛选单克隆抗体的示意图[32]

Fig. 3 Schematic diagram of monoclonal antibody screening based on single B cell technique[32]

图4 基于人工智能筛选治疗COVID-19候选药物的示意图[40]

Fig. 4 Schematic diagram of AI-based screening of drug candidates for COVID-19[40]

表1 不同类型抗体技术的优点与不足

Table 1 Advantages and disadvantages of different types of antibody technology

抗体筛选技术	优点	不足
抗体文库展示技术	获得全人源化抗体、文库基因来源灵活、筛选周期短	抗体库储存运输困难、重链与轻链非天然配对、易筛选到非特异性抗体
转基因小鼠技术	获得全人源化抗体、速度快、亲和力高	可能存在免疫耐受、不能排除鼠源抗体产生、技术壁垒高
单个B细胞抗体技术	获得全人源化抗体、高通量筛选、周期短，技术较成熟、重链与轻链天然配对	费用较高、操作严格、技术要求高、对抗原质量要求高、抗原特异性细胞的比例较低
AI 辅助药物开发技术	获得全人源化抗体、周期短、成本低、成功率高	数据库有待完善、相关数据很难全部整合在一起

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抗体药物筛选技术的研究进展

Research Progress of Antibody Drug Screening Technology

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