ABSTRACT

Introduction: The market for monoclonal antibody (mAb) therapies is growing rapidly as the pharmaceutical industry expands its development across a broad spectrum of diseases. Unfortunately, as shown in the recent failure of bococizumab by Pfizer, these treatments often stimulate the formation of problematic anti-drug antibodies (ADAs). ADAs can cause side effects and limit efficacy for many patients. To increase efficacy and decrease safety concerns from ADAs, immunogenicity characterization is needed early in the drug development process. Here, we present emerging techniques that hold promise to improve ADA assays and their potential applications to pharmaceutical development and personalized medicine.

Areas covered: This manuscript outlines the importance of epitope characterization to better understand immunogenicity and describes a strategy for using this information in treating patients taking mAb therapies.

Expert opinion: We propose using high-information assays to characterize epitopes to help mAb therapy engineering and potentially improve individual patient outcomes. To understand this, we will discuss three different aspects of ADAs: (1) the problem of ADAs and what is currently being done about them, (2) the current state of epitope characterization and how it is being utilized, and (3) how early epitope characterization can advance drug discovery and improve outcomes for patients taking mAb therapies.

摘要

简介：随着制药行业在广泛的疾病领域扩展其发展，单克隆抗体 (mAb) 疗法市场正在迅速增长。不幸的是，正如辉瑞公司最近对 bococizumab 的失败所表明的那样，这些治疗通常会刺激有问题的抗药物抗体 (ADA) 的形成。ADA 可能会导致副作用并限制许多患者的疗效。为了提高疗效并减少 ADA 的安全性问题，需要在药物开发过程的早期进行免疫原性表征。在这里，我们展示了有望改进 ADA 检测的新兴技术及其在药物开发和个性化医疗中的潜在应用。

涵盖的领域：本手稿概述了表位表征对更好地了解免疫原性的重要性，并描述了使用此信息治疗接受 mAb 疗法的患者的策略。

专家意见：我们建议使用高信息化验来表征表位，以帮助 mAb 治疗工程并可能改善个体患者的结果。为了理解这一点，我们将讨论 ADAs 的三个不同方面：(1) ADAs 的问题以及目前对它们所做的工作，(2) 表位表征的当前状态以及如何使用它，以及 (3) 如何早期表位表征可以促进药物发现并改善接受 mAb 治疗的患者的预后。