Stas Philippe, Lasters Ignace
Algonomics NV, Technologiepark 4, B-9052 Gent, Belgium.
IDrugs. 2009 Mar;12(3):169-73.
The immunogenicity assessment of protein therapeutics has received significant attention, both from regulatory bodies and industry. With the advent of several industry white papers and the EMEA guidance on the clinical assessment of antidrug antibodies (ADAs), the immunogenicity screening framework has become better defined. Immunogenicity in many cases leads to the loss of efficacy of a drug, but can also lead to the production of severe adverse effects. A risk assessment should be conducted for every biotherapeutic under development to address the incidence rate of immunogenicity, as well as the severity of the adverse effects caused. Typically, immunogenicity is characterized by measuring the ADAs that occur in individuals exposed to a drug. Industry and academic research efforts are geared toward the assessment of potential immunogenicity in a preclinical setting, with the aim of predicting immunogenicity prior to clinical trials, and thereby reducing the attrition rate of drugs in clinical development. This article addresses the current status, strategies and challenges related to the predictive immunogenicity assessment of protein therapeutics.
蛋白质治疗药物的免疫原性评估已受到监管机构和制药行业的高度关注。随着几份行业白皮书的问世以及欧洲药品管理局（EMEA）关于抗药物抗体（ADAs）临床评估的指南发布，免疫原性筛选框架已变得更加明确。在许多情况下，免疫原性会导致药物疗效丧失，但也可能导致严重不良反应的产生。对于正在研发的每一种生物治疗药物，都应进行风险评估，以确定免疫原性的发生率以及所引起不良反应的严重程度。通常，免疫原性通过检测接触药物个体中出现的抗药物抗体来表征。制药行业和学术研究致力于在临床前环境中评估潜在免疫原性，目的是在临床试验前预测免疫原性，从而降低临床开发中药物的淘汰率。本文阐述了与蛋白质治疗药物预测性免疫原性评估相关的现状、策略和挑战。
