Immunochemistry Department, PPD Laboratories, Richmond, VA, USA.
BioAnalytical Sciences, Genentech, Inc., South San Francisco, CA, USA.
AAPS J. 2020 Mar 17;22(3):60. doi: 10.1208/s12248-020-00440-5.
This article provides a theoretical case-study risk assessment report for a low-risk monoclonal antibody (mAb) therapeutic. In terms of risk, there are considerations around risks to safety, but also risks regarding effects on pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Much of the discussion in this document is around the risk of immunogenicity incidence. A higher incidence of immunogenicity would necessitate a detailed review of the PK, efficacy and safety in anti-drug antibody (ADA) positive and ADA negative subjects, in order to evaluate potential effects. The publication is intended to provide a framework of some the current thought processes around assessing immunogenicity risk and for building strategies to mitigate those risks. For this example, we have created a hypothetical antibody, ABC-123, targeting a membrane protein on antigen presenting cells, for the treatment of rheumatoid arthritis (RA). This hypothetical antibody therapeutic is provided as an example for the purposes of risk assessment for a low risk molecule, although any application of similar approach would be case by case.
本文提供了一个针对低风险单克隆抗体（mAb）治疗药物的理论案例研究风险评估报告。就风险而言，需要考虑安全性风险，还需要考虑对药代动力学（PK）、药效动力学（PD）和疗效的影响。本文档的大部分讨论都围绕着免疫原性发生率的风险。如果免疫原性发生率较高，则需要对 ADA 阳性和 ADA 阴性受试者中的 PK、疗效和安全性进行详细审查，以评估潜在影响。该出版物旨在提供一个评估免疫原性风险的当前思维框架，并制定减轻这些风险的策略。对于这个例子，我们创建了一个针对抗原呈递细胞上的膜蛋白的假设抗体 ABC-123，用于治疗类风湿关节炎（RA）。该假设的抗体治疗药物仅作为评估低风险分子风险的示例，尽管任何类似方法的应用都将是具体情况具体分析。
