Polsky Rodd, Gunn George, Reese Kimberly J, Hottenstein Charles Scott, Gehman Andrew, Schwartz Ann, Root Devin, Concannon Amy
GSK, Immunogenicity Group, Collegeville, PA 19426, USA.
Bioanalysis. 2024 Mar;16(5):277-287. doi: 10.4155/bio-2023-0184. Epub 2024 Feb 9.
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物抗体（ADA）的价值有限，因为非临床ADA的形成和发生率与临床经验并不相关。然而，非临床物种中ADA的形成和存在可能与药物暴露减少以及包括血管炎和免疫复合物疾病在内的安全性观察结果相关。用于人源化单克隆抗体生物治疗药物的通用ADA方法减少了在非临床药物开发过程中开发定制ADA方法的需求。已开发并验证了一种耐药物、灵敏的通用ADA免疫测定法，用于测量食蟹猴血清样本中的ADA，从而能够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可部署的方式区分复合ADA和游离ADA。
