Real-Time Analysis on Drug-Antibody Ratio of Antibody-Drug Conjugates for Synthesis, Process Optimization, and Quality Control
文献类型：期刊论文
| 作者 | Tang, Yubo1,2; Tang, Feng1; Yang, Yang1; Zhao, Lei1; Zhou, Hu1 ; Dong, Jinhua2; Huang, Wei1
|
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2017-08-10 |
| 卷号 | 7 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-017-08151-2 |
| 文献子类 | Article |
| 英文摘要 | Drug-antibody ratio (DAR) of antibody-drug conjugates (ADCs) is important for their therapeutic efficacy and pharmacokinetics, therefore control on DAR in synthesis process is a key for ADC quality control. Although various analytical methods were reported, the real-time monitoring on DAR is still a challenge because time-consuming sample preparation is usually needed during the analysis. Antibody deglycosylation of ADC simplifies DAR measurement, however long-time PNGaseF digestion for deglycosylation hampers the real-time detection. Here, we report a rapid DAR analysis within 15 min by robust deglycosylation treatment and LC-MS detection that enables real-time DAR monitoring for optimization on ADC synthetic process. With this approach, we were able to screen suitable conjugation conditions efficiently and afford the ADCs with expected DARs. To the best of our knowledge, this is the first report on real-time DAR analysis of ADCs for conjugation optimization and quality control, compatible with random lysine-linked ADCs, glycosite-specific ADCs, and the complicated dual-payload ADCs. |
| WOS关键词 | MASS-SPECTROMETRY ; LIQUID-CHROMATOGRAPHY ; THERAPEUTIC ANTIBODY ; LOAD DISTRIBUTION ; IN-VIVO ; DAR ; GLYCOSYLATION ; CHEMISTRY ; STRAIN ; LINKER |
| 资助项目 | National Natural Science Foundation of China (NNSFC)[21572244] ; National Natural Science Foundation of China (NNSFC)[21372238] ; SIMM institute fund[CASIMM0120153004] ; "Personalized Medicines: Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020311] ; Innovation Project of Instrument and Equipment Function Development from Chinese Academy of Sciences[YZ201542] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000407400200009 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272530]  |
| 专题 | 生物技术药物研发中心（筹） 药物安全性评价中心 |
| 通讯作者 | Dong, Jinhua; Huang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Liaoning, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Tang, Yubo,Tang, Feng,Yang, Yang,et al. Real-Time Analysis on Drug-Antibody Ratio of Antibody-Drug Conjugates for Synthesis, Process Optimization, and Quality Control[J]. SCIENTIFIC REPORTS,2017,7. |
| APA | Tang, Yubo.,Tang, Feng.,Yang, Yang.,Zhao, Lei.,Zhou, Hu.,...&Huang, Wei.(2017).Real-Time Analysis on Drug-Antibody Ratio of Antibody-Drug Conjugates for Synthesis, Process Optimization, and Quality Control.SCIENTIFIC REPORTS,7. |
| MLA | Tang, Yubo,et al."Real-Time Analysis on Drug-Antibody Ratio of Antibody-Drug Conjugates for Synthesis, Process Optimization, and Quality Control".SCIENTIFIC REPORTS 7(2017). |
入库方式： OAI收割
来源：上海药物研究所
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