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Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum

文献类型：期刊论文

作者Liu, Tingting5; Sun, Yajun4; Deng, Xiaojie5; Shi, Lili4; Chen, Wenyi5; Fang, Wenjing5; Wu, Junliang5; Fan, Xiaotian5; Chen, Xiaoqiang5; Sun, Jianhua5
刊名MOLECULES
出版日期2023-02-01
卷号28期号:4页码:1684
关键词antibody-drug conjugate immunogenicity anti-drug antibody bridging ELISA
DOI10.3390/molecules28041684
文献子类Article
英文摘要Immunogenicity is a major issue associated with the PK, efficacy, and safety evaluation of therapeutic protein products during pre-clinical and clinical studies. A multi-tiered approach consisting of screening, confirmatory, and titration assays has been widely adopted for anti-drug antibody testing. GQ1001, a recombinant humanized anti-human epidermal growth factor receptor 2 monoclonal antibody covalently linked to a cytotoxin of DM1, possesses a novel format of antibody-drug conjugates. In this study, we reported the development, validation, and application of an acid-dissociation bridging enzyme-linked immunosorbent assay for the detection of antibodies against GQ1001 in cynomolgus monkey serum. The sensitivity of the screening assay was 126.141 ng/mL in undiluted serum. The screening assay and confirmatory assay were neither affected by the naive monkey serum nor by 2% and 5% (v/v) erythrocyte hemolysates. Moreover, the assay was not subject to interference by 2500 ng/mL of human IgG1 in the samples. Drug interference at low positive control (150 ng/mL) and high positive control (8000 ng/mL) of anti-GQ1001 antibodies was not observed when GQ1001 concentrations were below 3.125 mu g/mL and 100 mu g/mL, respectively. Furthermore, no hook effect was observed for the positive antibodies in the concentration range of 8 to 64 mu g/mL. The validated assay was, thereafter, successfully applied to a single-dose toxicity study of GQ1001. Anti-drug antibody positive rates among dosing animals and testing samples were reported, and no significant impact was found on toxicokinetic outcomes.
WOS关键词THERAPEUTIC PROTEINS ; IMMUNOGENICITY
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
出版者MDPI
WOS记录号WOS:000940990000001
源URL[http://119.78.100.183/handle/2S10ELR8/309710]  
专题新药研究国家重点实验室
通讯作者Qin, Gang; Gong, Likun; 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, Sch Pharm, Beijing 100049, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
4.GeneQuantum Healthcare Suzhou Co Ltd, Suzhou 215000, 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		 Liu, Tingting,Sun, Yajun,Deng, Xiaojie,et al. Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum[J]. MOLECULES,2023,28(4):1684.
APA Liu, Tingting.,Sun, Yajun.,Deng, Xiaojie.,Shi, Lili.,Chen, Wenyi.,...&Qin, Qiuping.(2023).Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum.MOLECULES,28(4),1684.
MLA Liu, Tingting,et al."Development, Validation and Application of a Bridging ELISA for Detection of Antibodies against GQ1001 in Cynomolgus Monkey Serum".MOLECULES 28.4(2023):1684.

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来源：上海药物研究所

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