Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments.

IF 7.3 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
mAbs Pub Date : 2025-12-01 Epub Date: 2025-02-01 DOI:10.1080/19420862.2025.2458627
Yun Hee Jeong, Gillian Lennon, Geertruida Veldman, Daniel M Serna, Alexander Ibrahimov
{"title":"Establishing endotoxin limits to enhance the reliability of in vitro immunogenicity risk assessments.","authors":"Yun Hee Jeong, Gillian Lennon, Geertruida Veldman, Daniel M Serna, Alexander Ibrahimov","doi":"10.1080/19420862.2025.2458627","DOIUrl":null,"url":null,"abstract":"<p><p>Immunogenic responses to biotherapeutics often lead to termination of their development because the resulting anti-drug-antibodies (ADA) can negatively impact pharmacology, safety, and efficacy. To mitigate ADA risks, in vitro risk assessment assays in non-clinical settings are essential to enhance safety and efficacy of protein-based therapeutics. This study aimed to develop and validate a human <i>in vitro</i> immunogenicity T cell proliferation assay. However, there is a lack of comprehensive guidelines for managing product-related factors such as endotoxin contamination, which can significantly influence assay sensitivity and accuracy. Our investigation of the impact of endotoxins revealed that levels above 0.1 EU/mg significantly induce T cell proliferation and CD14<sup>+</sup> myeloid cell expansion, leading to potential false-positive outcomes in immunogenicity assessments. These findings suggest the importance of developing standardized protocols to enhance the predictive capability of in vitro methods, ensuring the assessment of therapeutic proteins accurately reflects their immunogenic potential without interference from contaminants.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2458627"},"PeriodicalIF":7.3000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792839/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"mAbs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19420862.2025.2458627","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Immunogenic responses to biotherapeutics often lead to termination of their development because the resulting anti-drug-antibodies (ADA) can negatively impact pharmacology, safety, and efficacy. To mitigate ADA risks, in vitro risk assessment assays in non-clinical settings are essential to enhance safety and efficacy of protein-based therapeutics. This study aimed to develop and validate a human in vitro immunogenicity T cell proliferation assay. However, there is a lack of comprehensive guidelines for managing product-related factors such as endotoxin contamination, which can significantly influence assay sensitivity and accuracy. Our investigation of the impact of endotoxins revealed that levels above 0.1 EU/mg significantly induce T cell proliferation and CD14+ myeloid cell expansion, leading to potential false-positive outcomes in immunogenicity assessments. These findings suggest the importance of developing standardized protocols to enhance the predictive capability of in vitro methods, ensuring the assessment of therapeutic proteins accurately reflects their immunogenic potential without interference from contaminants.

Abstract Image

Abstract Image

Abstract Image

建立内毒素限度以提高体外免疫原性风险评估的可靠性。
对生物疗法的免疫原性反应常常导致其发展的终止,因为由此产生的抗药物抗体(ADA)会对药理学、安全性和有效性产生负面影响。为了降低ADA风险,非临床环境下的体外风险评估分析对于提高基于蛋白质的治疗的安全性和有效性至关重要。本研究旨在建立和验证人类体外免疫原性T细胞增殖试验。然而,缺乏管理产品相关因素(如内毒素污染)的综合指南,内毒素污染会显著影响测定的灵敏度和准确性。我们对内毒素影响的研究表明,0.1 EU/mg以上的内毒素水平显著诱导T细胞增殖和CD14+骨髓细胞扩增,导致免疫原性评估的潜在假阳性结果。这些发现表明制定标准化方案以增强体外方法的预测能力的重要性,确保治疗蛋白的评估准确反映其免疫原性潜力,而不受污染物的干扰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
mAbs
mAbs 工程技术-仪器仪表
CiteScore
10.70
自引率
11.30%
发文量
77
审稿时长
6-12 weeks
期刊介绍: mAbs is a multi-disciplinary journal dedicated to the art and science of antibody research and development. The journal has a strong scientific and medical focus, but also strives to serve a broader readership. The articles are thus of interest to scientists, clinical researchers, and physicians, as well as the wider mAb community, including our readers involved in technology transfer, legal issues, investment, strategic planning and the regulation of therapeutics.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信