生物治疗过程开发过程中宿主细胞蛋白质的免疫信息学风险评估。

IF 5 3区 医学 Q1 PHARMACOLOGY & PHARMACY AAPS Journal Pub Date : 2023-09-11 DOI:10.1208/s12248-023-00852-z
Kirk Haltaufderhyde, Brian J Roberts, Sundos Khan, Frances Terry, Christine M Boyle, Mitchell McAllister, William Martin, Amy Rosenberg, Anne S De Groot
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引用次数: 0

摘要

从生物制品中鉴定和去除宿主细胞蛋白是药物开发的关键步骤。尽管纯化工艺最近有所改进,但在一系列细胞系中生产并使用不同工艺纯化的生物制品,如单克隆抗体、酶替代疗法和疫苗,可能含有HCP杂质,这使得开发人员有必要在每种药物产品的工艺开发过程中识别和量化杂质。含有与人类同源物不太保守的序列的HCP可能比那些更保守的序列更具免疫原性。我们开发了一种计算工具ISPRI-HCP,通过评估和量化人类蛋白质组中T细胞表位密度和与类似T细胞表位数的相对保守性来估计HCP序列的免疫原性潜力。在这里,我们描述了几个支持使用这种方法根据其免疫原性风险对候选HCP杂质进行分类的案例研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Immunoinformatic Risk Assessment of Host Cell Proteins During Process Development for Biologic Therapeutics.

The identification and removal of host cell proteins (HCPs) from biologic products is a critical step in drug development. Despite recent improvements to purification processes, biologics such as monoclonal antibodies, enzyme replacement therapies, and vaccines that are manufactured in a range of cell lines and purified using diverse processes may contain HCP impurities, making it necessary for developers to identify and quantify impurities during process development for each drug product. HCPs that contain sequences that are less conserved with human homologs may be more immunogenic than those that are more conserved. We have developed a computational tool, ISPRI-HCP, that estimates the immunogenic potential of HCP sequences by evaluating and quantifying T cell epitope density and relative conservation with similar T cell epitopes in the human proteome. Here we describe several case studies that support the use of this method for classifying candidate HCP impurities according to their immunogenicity risk.

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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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