Rodd Polsky, George Gunn, Kimberly J Reese, Charles Scott Hottenstein, Andrew Gehman, Ann Schwartz, Devin Root, Amy Concannon
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引用次数: 0
Abstract
The measurement of antidrug antibodies (ADA) in nonclinical studies provides limited value because the formation and incidence of nonclinical ADA does not translate to clinical experience. The formation and presence of ADA in nonclinical species can, however, correlate to reduced drug exposure and safety observations including vasculitis and immune complex disease. Generic ADA methods for humanized monoclonal antibody biotherapeutics mitigate the need to develop bespoke ADA methods during nonclinical drug development. A drug-tolerant, sensitive, generic ADA immunoassay has been developed and validated for measuring ADA in cynomolgus monkey serum samples, allowing for immediate qualification of future monoclonal antibody biotherapeutics. This approach allows us to differentiate complexed and free ADA in a rapidly deployable manner when needed.
在非临床研究中测量抗药抗体（ADA）的价值有限，因为非临床 ADA 的形成和发生率并不能转化为临床经验。不过，非临床物种中 ADA 的形成和存在可能与药物暴露减少和安全性观察（包括血管炎和免疫复合物疾病）相关。用于人源化单克隆抗体生物治疗药物的通用 ADA 方法减轻了在非临床药物开发过程中开发定制 ADA 方法的需要。我们开发并验证了一种耐药性强、灵敏度高的通用 ADA 免疫测定法，可用于测量猕猴血清样本中的 ADA，从而可对未来的单克隆抗体生物治疗药物立即进行鉴定。这种方法使我们能够在需要时以快速部署的方式区分络合 ADA 和游离 ADA。
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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