Hoofring Sarah A, Lopez Rocio, Hock M Benjamin, Kaliyaperumal Arunan, Patel Sonal K, Swanson Steven J, Chirmule Narendra, Starcevic Marta
Clinical Immunology, Amgen Inc., One Amgen Center Drive, 30E-3-B, Thousand Oaks, CA 91320, USA.
Bioanalysis. 2013 May;5(9):1041-55. doi: 10.4155/bio.13.10.
Immunogenicity testing is an important component of clinical development for large-molecule biotherapeutics. New complex types of large molecules, such as antibody-drug conjugates (ADCs), require careful evaluation of the testing strategy and bioanalytical assays used to monitor the development of antitherapeutic antibodies.
An electrochemiluminescence-based immunoassay for the detection and epitope characterization of anti-ADC antibodies was validated. Using this assay format, antibodies directed against the monoclonal antibody and linker-drug components of the ADC were successfully detected in a multiple-dose rat toxicity study.
Immunogenicity assays incorporating epitope determination may provide additional information about the characteristics of induced antitherapeutic antibodies, including the magnitude and timing of the various types of antibody responses.
免疫原性检测是大分子生物治疗药物临床开发的重要组成部分。新型复杂类型的大分子，如抗体药物偶联物（ADC），需要仔细评估用于监测抗治疗性抗体产生的检测策略和生物分析方法。
一种基于电化学发光的免疫分析方法被验证用于检测抗ADC抗体并确定其表位特征。采用这种分析形式，在一项多剂量大鼠毒性研究中成功检测到了针对ADC单克隆抗体和连接子-药物成分的抗体。
结合表位测定的免疫原性分析可能会提供有关诱导产生的抗治疗性抗体特征的额外信息，包括各类抗体反应的强度和时间。
