| 组织交叉试验中多路径体系技术难点的探索和研究 |
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| 引用本文： | 祁德波,王新国,富欣,李旻,邢萌,李欣,李华.组织交叉试验中多路径体系技术难点的探索和研究[J].现代药物与临床,2017,40(10):1372-1377. |
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| 作者姓名： | 祁德波 王新国 富欣 李旻 邢萌 李欣 李华 |
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| 作者单位： | 济南金域医学检验中心有限公司, 山东 济南 250100,济南金域医学检验中心有限公司, 山东 济南 250100,国家上海新药安全评价研究中心, 上海 201203,国家上海新药安全评价研究中心, 上海 201203,济南金域医学检验中心有限公司, 山东 济南 250100,济南金域医学检验中心有限公司, 山东 济南 250100,国家上海新药安全评价研究中心, 上海 201203 |
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| 基金项目： | “十二五”重大专项定向择优（2015ZX09501004-002-006和2015ZX09501-007-003）；上海市新药安全评价专业技术服务平台（15DZ2290300）；上海市浦东新区科委CRO项目（PKF2014-C01） |
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| 摘 要： | 组织交叉反应（tissue cross reactivity，TCR）是单克隆抗体药物开发过程中临床前安全评价的重要组成部分。TCR试验的目的是发现单抗药物和靶抗原以外表位结合，为体内试验毒副作用的监控提供参考。按照FDA、EMA和CFDA要求，TCR需在新药临床申请Ⅰ期临床试验前完成。近年随着单克隆抗体研发由鼠源型向全人源化单抗的转变和发展，免疫组织化学在很多技术环节上出现了新的问题和挑战。结合自身实际工作的经验和近年来国内外组织交叉反应研究的进展，探讨并总结单抗药物研发中TCR试验中的相多路径体系技术难点的探索和研究经验，期望能为进一步提高我国TCR试验质量，并增加TCR试验对体内毒理学评价及安全用药的参考价值提供一定的参考。
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| 关 键 词： | 单克隆抗体 组织交叉反应 免疫组织化学 技术难点 |
| 收稿时间： | 2017/7/10 0:00:00 |
Exploration on technical difficulties of multipath system in tissue cross-reactivity studies |
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| QI De-bo,WANG Xin-guo,FU Xin,LI Min,XING Meng,LI Xin and LI Hua.Exploration on technical difficulties of multipath system in tissue cross-reactivity studies[J].Drugs & Clinic,2017,40(10):1372-1377. |
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| Authors: | QI De-bo WANG Xin-guo FU Xin LI Min XING Meng LI Xin and LI Hua |
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| Institution: | Jinan Kingmed Diagnostics, Jinan 250101, China,Jinan Kingmed Diagnostics, Jinan 250101, China,National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai 201203, China,National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai 201203, China,Jinan Kingmed Diagnostics, Jinan 250101, China,Jinan Kingmed Diagnostics, Jinan 250101, China and National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai 201203, China |
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| Abstract: | Tissue cross-reactivity (TCR) studies play an important role in the preclinical safety evaluation of monoclonal antibody (mAb) drugs. The objective of TCR studies is to find out off-target binding sites of mAbs, and provide valuable predictions for the toxicological evaluation and safety medication in vivo. According to the new drug application requirements of FDA, EMA and CFDA, TCR studies need to be carried out before Phase I clinic trails. As the origin of mAb drugs was transferred from murine antibodies to fully humanized antibodies in current years, immunohistochemical methods used in TCR studies were confronted with some new problems and challenges. Taking our own experiences and recent progress on TCR studies at home and abroad together, the authors summarized the recent exploration on technical difficulties of multipath system in TCR studies. This may provide valuable insight for further improving the quality of TCR studies and increase the predictive value of TCR studies for in vivo toxicological evaluation in China. |
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| Keywords: | monoclonal antibodies tissue cross-reactivity immunohistochemistry technical difficulties |
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