分析灵敏度
药品
药物开发
抗体
计算生物学
阳性对照
药理学
独特型
生物
医学
免疫学
单克隆抗体
病理
替代医学
传统医学
作者
Joshua A. Weiner,Harini Natarajan,C. McIntosh,Eun Sung Yang,Misook Choe,Cassidy L. Papia,Katherine S. Axelrod,Gabriela Kovacikova,Amarendra Pegu,Margaret E. Ackerman
标识
DOI:10.1016/j.jim.2024.113657
摘要
Development of assays to reliably identify and characterize anti-drug antibodies (ADAs) depends on positive control anti-idiotype (anti-id) reagents, which are used to demonstrate that the standards recommended by regulatory authorities are met. This work employs a set of therapeutic antibodies under clinical development and their corresponding anti-ids to investigate how different positive control reagent properties impact ADA assay development. Positive controls exhibited different response profiles and apparent assay analytical sensitivity values depending on assay format. Neither anti-id affinity for drug, nor sensitivity in direct immunoassays related to sensitivity in ADA assays. Anti-ids were differentially able to detect damage to drug conjugates used in bridging assays and were differentially drug tolerant. These parameters also failed to relate to assay sensitivity, further complicating selection of anti-ids for use in ADA assay development based on functional characteristics. Given this variability among anti-ids, alternative controls that could be employed across multiple antibody drugs were investigated as a more uniform means to define ADA detection sensitivity across drug products and assay protocols, which could help better relate assay results to clinical risks of ADA responses. Overall, this study highlights the importance of positive control selection to reliable detection and clinical interpretation of the presence and magnitude of ADA responses.
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