Purpose

Biotherapeutics are a large and rapidly growing class of drugs being produced by pharmaceutical companies to treat a diverse range of clinical indications. The overall efficacy and safety of these products can be greatly impacted by their capacity to induce undesired immune responses. This review discusses in vitro cell-based methods used to assess the T cell mediated immunogenicity risk of proteinaceous therapeutic modalities and manufacturing impurities.

Methods

Here, we outline the potential sources and factors that influence immunogenicity. We present patient and product considerations that should be made in designing appropriate in vitro experiments that evaluate T cell epitopes capable of triggering treatment and outcome impacting anti-drug antibody responses and other adverse events.

Results

We present the current in vitro assays used to assess T cell activation towards biotherapeutics and the product impurities. Lastly, we outline the caveats, concerns, and challenges that remain with these cell-based assays.

Conclusions

Data generated from these in vitro antigenicity/immunogenicity assays may be used to derive immunogenicity risk assessments for programs and production processes and provides an opportunity for early selection of candidates or manufacturing impurities with lower likelihood of generating or exacerbating clinical immunogenicity.

中文翻译：

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目前用于预测T细胞介导的生物疗法免疫原性和制造杂质的体外分析

目的

生物治疗学是制药公司生产的用于治疗各种临床适应症的一大类且正在快速增长的药物。这些产品诱导不希望的免疫反应的能力会极大地影响这些产品的整体功效和安全性。这篇综述讨论了基于体外细胞的方法，该方法用于评估T细胞介导的蛋白质治疗方式和制造杂质的免疫原性风险。

方法

在这里，我们概述了影响免疫原性的潜在来源和因素。我们介绍了在设计合适的体外实验时应考虑的患者和产品考虑因素，这些实验应评估能够触发治疗并影响抗药物抗体反应和其他不良事件的T细胞表位。

结果

我们介绍了当前的体外测定法，用于评估T细胞对生物治疗剂和产品杂质的活化。最后，我们概述了这些基于细胞的测定法所存在的警告，关注和挑战。

结论

从这些体外抗原性/免疫原性测定产生的数据可用于得出程序和生产过程的免疫原性风险评估，并为早期选择候选对象或制造杂质提供了机会，从而降低了产生或加剧临床免疫原性的可能性。