Development and Validation of an ADA-Tolerant Assay for Quantification of an Exatecan-Based ADC in Monkey Plasma
文献类型：期刊论文
| 作者 | Tao, Yimin1,2; Lu, Wei7; Gao, Jinli1,2; Yang, Shuangshuang1,2 ; Ruan, Chaoyi1,2; Hou, Yingying1,2; Lu, Jing1,2; Xu, Junjiu1,2; Zhang, Jianjian6; Pasas-Farmer, Stephanie5
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| 刊名 | MOLECULES
 |
| 出版日期 | 2024-02-01 |
| 卷号 | 29期号:3页码:14 |
| 关键词 | antibody-drug conjugate (ADC) bioanalysis anti-drug antibody (ADA) ligand binding assay (LBA) ADA-tolerant assay |
| DOI | 10.3390/molecules29030572 |
| 通讯作者 | Qin, Qiuping(qpqin@cdser.simm.ac.cn) ; Gong, Likun(lkgong@cdser.simm.ac.cn) |
| 英文摘要 | Background: The development of an anti-drug antibody (ADA)-tolerant pharmacokinetic (PK) assay is important when the drug exposure is irrelevant to toxicity in the presence of ADA. We aimed to develop and validate an ADA-tolerant assay for an exatecan-based antibody-drug conjugate (ADC) in monkey plasma. Results: The assay tolerated 5.00 mu g/mL of ADA at 12 mu g/mL of ADC. Its accuracy and precision results satisfied the acceptance criteria. Furthermore, the assay was free from hook and matrix effects and exhibited good dilutional linearity. Additionally, the ADC in plasma samples was stable under different storage conditions. Method: An ADA-tolerant ADC assay was configured with an anti-payload antibody for capture, and a drug-target protein combined with a horseradish peroxidase (HRP)-labeled antibody against a drug-target-protein tag for detection. Samples were firstly acidified to dissociate drug and ADA complexes, and to convert the carboxylate form to the lactone form of exatecan molecules; then, the ADAs in the samples were removed with a naked antibody-coated microplate. The treated samples were further incubated with coated anti-payload antibody and captured ADC molecules were quantified by the detection reagent. The developed assay was optimized and validated against regulatory guidelines. Conclusions: The assay met both methodological and sample-related ADA tolerance requirements, and was applicable to a nonclinical study in cynomolgus monkeys. |
| WOS关键词 | CAMPTOTHECIN ; IMPACT ; BIOANALYSIS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| 出版者 | MDPI |
| WOS记录号 | WOS:001160230700001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309204]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Qin, Qiuping; Gong, Likun |
| 作者单位 | 1.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan 528400, Peoples R China 4.Univ Chinese Acad Sci, Beijing 101408, Peoples R China 5.BioData Solut LLC, Lawrence, KS 66044 USA 6.Multitude Therapeut Inc, Shanghai 200233, Peoples R China 7.OnCusp Therapeut, New York, NY 10013 USA |
| 推荐引用方式 GB/T 7714 | Tao, Yimin,Lu, Wei,Gao, Jinli,et al. Development and Validation of an ADA-Tolerant Assay for Quantification of an Exatecan-Based ADC in Monkey Plasma[J]. MOLECULES,2024,29(3):14. |
| APA | Tao, Yimin.,Lu, Wei.,Gao, Jinli.,Yang, Shuangshuang.,Ruan, Chaoyi.,...&Gong, Likun.(2024).Development and Validation of an ADA-Tolerant Assay for Quantification of an Exatecan-Based ADC in Monkey Plasma.MOLECULES,29(3),14. |
| MLA | Tao, Yimin,et al."Development and Validation of an ADA-Tolerant Assay for Quantification of an Exatecan-Based ADC in Monkey Plasma".MOLECULES 29.3(2024):14. |
入库方式： OAI收割
来源：上海药物研究所
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