PD-1/PD-L1免疫检查点抗体药物制剂稳定性开发

doi:10.13523/j.cb.2005048

中国生物工程杂志

2020, Vol. 40

Issue (10): 35-42 DOI: 10.13523/j.cb.2005048

综述

PD-1/PD-L1免疫检查点抗体药物制剂稳定性开发

吝建华¹,韩君^2,^*,徐寒梅^1,^*

1 中国药科大学南京 211198
2 天士力生物医药股份有限公司上海 201203

Developing the Stability of PD-1 / PD-L1 Immune Checkpoint Antibody Drug Formulation

LIN Jian-hua¹,HAN Jun^2,^*,Xu Han-mei^1,^*

1 China Pharmaceutical University, Nanjing 211198, China
2 Tasly Biopharmaceuticals Co., Ltd., Shanghai 201203, China

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摘要：

近年来抗体药物在生物医药领域发展迅速。随着抗体疗法种类的不断增加和PD-1/PD-L1靶点蛋白结构的确证,临床上,越来越多针对PD-1/PD-L1免疫检查点的单克隆抗体药物被不断开发并应用于治疗死亡率高、治愈率低的多种癌症中。但是抗体药物制剂开发水平还需进一步提高,一方面同一靶点的抗体产品同质化严重,另一方面抗体药物的理化性质比小分子药物复杂,因此需要针对不同单克隆抗体的药物特性,筛选出适应于临床应用的稳定蛋白制剂处方。概括了不同抗体药物制剂处方成分(缓冲液成分、药物辅料)的作用,结合PD-1/PD-L1靶点介绍了抗体药物制剂稳定性开发的一般策略以及CDE相关的审评要点。

关键词： 免疫检查点PD-1/PD-L1; 单克隆抗体药物; 制剂处方; 稳定性

Abstract:

Recently, antibody drugs have developed rapidly in the field of biopharmaceuticals. Clinically, the type and number of monoclonal antibody-based tumor therapies are increasing. With confirmed structure of PD-1/PD-L1 protein,monoclonal antibody drugs against immune checkpoint PD-1/PD-L1 have been continuously developed and applied to the treatment of many principal cancers with high mortality and low cure rate. However, due to the complex physical and chemical properties and serious homogenization, monoclonal antibody drugs are necessary to screen out stable protein preparations for clinical applications based on the characteristics of different monoclonal antibody drugs. This article reviews the role of different antibody drug formulations (buffer components, drug excipients), combined with the PD-L1 target, which introduces the stability development of antibody drug formulations and the main points for evaluation of CDE.

Key words: Immune checkpoint PD-1/PD-L1 mAb Formulation Stability

收稿日期: 2020-05-22 出版日期: 2020-11-10

ZTFLH:

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通讯作者: 韩君,徐寒梅

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引用本文:

吝建华,韩君,徐寒梅. PD-1/PD-L1免疫检查点抗体药物制剂稳定性开发[J]. 中国生物工程杂志, 2020, 40(10): 35-42.

LIN Jian-hua,HAN Jun,Xu Han-mei. Developing the Stability of PD-1 / PD-L1 Immune Checkpoint Antibody Drug Formulation. China Biotechnology, 2020, 40(10): 35-42.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2005048 或 https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I10/35

图1 免疫球蛋白结构和常见抗体类型

表1 影响蛋白稳定性的主要因素[20]

表2 商品化的PD-1/PD-L1的单克隆抗体制剂汇总表

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