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。
BioanalysisBIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
3.30
自引率
16.70%
发文量
88
审稿时长
2 months
期刊介绍：
Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing.
The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality.
Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing.
The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques.
Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.
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