Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb, Waltham, Massachusetts, USA.
Biologics and Vaccine Formulations, Merck Sharp & Dohme Corp, 2000 Galloping Hill Road, K-15 H406, Kenilworth, New Jersey, 07033, USA.
AAPS J. 2017 Nov;19(6):1587-1592. doi: 10.1208/s12248-017-0143-z. Epub 2017 Oct 2.
In silico HLA-binding algorithms and in vitro T cell-based assays as predictive tools for human immunogenicity risk have made inroads in the biotherapeutic drug discovery and development process. Currently, these tools are being used only for candidate selection or characterization and not for making a go/no-go decision for further development. A clear limitation for a broader implementation is the lack of correlation between the predicted T cell epitope content/immune reactivity potential of a biotherapeutic and the subsequent ADA-related clinical immunogenicity outcome. The current state of technologies and their pros and cons were discussed as a part of the 2016 AAPS National Biotechnology Conference in a themed session. A review of the advances in the area and the session talks along with the ensuing discussions are summarized in this commentary.
基于计算机的 HLA 结合算法和基于体外 T 细胞的检测作为预测人类免疫原性风险的工具，已经在生物治疗药物的发现和开发过程中取得了进展。目前，这些工具仅用于候选物的选择或表征，而不能用于对进一步开发做出去留的决定。广泛应用的一个明显限制是生物治疗的预测 T 细胞表位含量/免疫反应潜能与随后的 ADA 相关临床免疫原性结果之间缺乏相关性。作为 2016 年 AAPS 国家生物技术会议主题会议的一部分，讨论了当前技术的优缺点。本文对该领域的进展以及会议演讲和随后的讨论进行了综述。
