Kellie John F, Tran John C, Jian Wenying, Jones Barry, Mehl John T, Ge Ying, Henion Jack, Bateman Kevin P
Bioanalysis, Immunogenicity & Biomarkers, GlaxoSmithKline, Collegeville, Pennsylvania 19426, United States.
Biochemical & Cellular Pharmacology, Genentech Inc., South San Francisco, California 94080, United States.
J Am Soc Mass Spectrom. 2021 Aug 4;32(8):1886-1900. doi: 10.1021/jasms.0c00270. Epub 2020 Sep 15.
Recent advancements in immunocapture methods and mass spectrometer technology have enabled intact protein mass spectrometry to be applied for the characterization of antibodies and other large biotherapeutics from in-life studies. Protein molecules have not been traditionally studied by intact mass or screened for catabolites in the same manner as small molecules, but the landscape has changed. Researchers have presented methods that can be applied to the drug discovery and development stages, and others are exploring the possibilities of the new approaches. However, a wide variety of options for assay development exists without clear recommendation on best practice, and data processing workflows may have limitations depending on the vendor. In this perspective, we share experiences and recommendations for current and future application of mass spectrometry for biotherapeutic molecule monitoring from preclinical and clinical studies.
免疫捕获方法和质谱技术的最新进展使完整蛋白质质谱能够应用于在研研究中抗体和其他大型生物治疗药物的表征。传统上，蛋白质分子尚未像小分子那样通过完整质量进行研究或筛选其分解代谢物，但情况已经发生了变化。研究人员已经提出了可应用于药物发现和开发阶段的方法，其他人员也在探索新方法的可能性。然而，存在各种各样的分析方法开发选项，却没有关于最佳实践的明确建议，并且数据处理工作流程可能因供应商而异存在局限性。从这个角度出发，我们分享关于质谱在临床前和临床研究中生物治疗分子监测的当前及未来应用的经验和建议。
