化学改性治疗蛋白质在临床开发中的免疫性评估策略
Charlotte Hagman1, Gaetan Chasseigne1, Robert Nelson2
1Pharmacokinetic Sciences - Drug Disposition, Biomedical Research, Novartis, Basel, Switzerland.
Frontiers in immunology
|November 26, 2024
概括
评估转基因生物制剂的免疫性是复杂的. 在临床试验中,使用广泛表征的新策略有效监测了抗药抗体 (ADA) 和中和抗体 (NAbs).
科学领域:
- 生物制药的发展.
- 免疫学 免疫学 免疫学
- 分析化学是一种分析化学.
背景情况:
- 评估复杂的,化学改性生物制剂的免疫性提出了重要的生物分析挑战.
- 现有的方法可能无法完全捕捉对多域蛋白疗法的细微免疫反应.
研究的目的:
- 开发和验证一个全面的策略,以评估抗药抗体 (ADA) 与新型化学修饰蛋白疗法.
- 在临床试验中使用以风险为中心的分层方法评估免疫反应,并进行广泛的表征.
主要方法:
- 实施了一种以风险为中心的新策略,包括对ADS的标准查和确认试验.
- 开发和验证了广泛的特征测试,包括定位,表位图绘制 (抗GDF15,抗PEG脂肪酸) 和基于细胞的中和测试.
- 分析方法应用于两项临床试验的样本,其中包括健康志愿者和超重/肥胖患者.
主要成果:
- 观察到抗药抗体 (ADA) 的发病率较低.
- 针对聚乙烯糖醇 (PEG) 与脂肪酸结合的链接剂,没有检测到ADA.
- 在一项临床研究中确定了中和ADAs.
结论:
- 提出的广泛表征的新策略对于监测ADA和中和抗药抗体 (NAbs) 是有效的.
- 这种方法可以支持化学修饰蛋白质和多域生物治疗的临床开发.
- 该战略解决了免疫性评估中的关键生物分析挑战.
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