中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Development of an ELISA with acidification treatment for an antibody conjugate incorporating Exatecans

文献类型:期刊论文

作者Zhang, Yingying4,5; Yun, Xi5; Ouyang, Lu5; Zhang, Xianjing5; Gong, Likum1,2,3,4,5; Qin, Qiuping5
刊名ANALYTICAL BIOCHEMISTRY
出版日期2024-07-01
卷号690页码:8
关键词Antibody-drug conjugate Camptothecin Exatecan Bioanalysis Pharmacokinetics
ISSN号0003-2697
DOI10.1016/j.ab.2024.115530
通讯作者Gong, Likum(lkgong@cdser.simm.ac.cn) ; Qin, Qiuping(qpqin@cdser.simm.ac.cn)
英文摘要The successful development of Sacituzumab Govitecan and Trastuzumab Deruxtecan has made camptothecin derivatives one of the most popular payloads for antibody-drug conjugates (ADCs). Camptothecin and its derivatives all exist in a pH-dependent equilibrium between the carboxylate and lactone forms. Such transformation may lead to differences in the ratio of the two molecular forms in calibration standards and biological matrix (bio-matrix) samples, thereby leading to inaccurate conjugated antibody results. In this study, we reported an enzyme-linked immunosorbent assay (ELISA) free of the aforementioned influence for the detection of the Exatecans-conjugated antibody (conjugated SM001) in cynomolgus monkey serum. The assay was developed by first acidifying all samples with glacial acetic acid (HAc), then performing neutralization and thereafter capturing conjugated SM001 with anti-Exatecan monoclonal antibody (mAb) and detecting it with biotinylated Nectin4 (hNectin4-Bio) and horseradish peroxidase-labeled streptavidin (SA-HRP). Results showed that all tested performance parameters met the acceptance criteria. The conjugated SM001 concentrations obtained were in parallel to but slightly lower than total antibody (TAb) throughout the pharmacokinetic (PK) study, revealing that the assay strategy implemented for conjugated SM001 measurement worked well for the elimination of interference triggered by the heterogeneous existence of the lactone and carboxylate forms of Exatecan (lactoneExatecan and carboxylate-Exatecan).
WOS关键词SACITUZUMAB GOVITECAN ; TOPOISOMERASE-I ; CAMPTOTHECIN
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:001227551600001
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/311063]  
专题新药研究国家重点实验室
通讯作者Gong, Likum; Qin, Qiuping
作者单位1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
2.Univ Chinese Acad Sci, Beijing 101408, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Nanjing Univ Chinese Med, Nanjing 210023, Jiangsu Provinc, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Dept Immunoassay & Immunochem, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Yingying,Yun, Xi,Ouyang, Lu,et al. Development of an ELISA with acidification treatment for an antibody conjugate incorporating Exatecans[J]. ANALYTICAL BIOCHEMISTRY,2024,690:8.
APA Zhang, Yingying,Yun, Xi,Ouyang, Lu,Zhang, Xianjing,Gong, Likum,&Qin, Qiuping.(2024).Development of an ELISA with acidification treatment for an antibody conjugate incorporating Exatecans.ANALYTICAL BIOCHEMISTRY,690,8.
MLA Zhang, Yingying,et al."Development of an ELISA with acidification treatment for an antibody conjugate incorporating Exatecans".ANALYTICAL BIOCHEMISTRY 690(2024):8.

入库方式: OAI收割

来源:上海药物研究所

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