阳性对照的结合性对抗药物抗体测定性能的影响
Trinidad Arceo1, Ben Andrews1, Jennifer Getz1
1BioAnalytical Sciences, Genentech, South San Francisco, CA, USA.
对抗药物抗体 (ADA) 测试中的正控测试显著影响测试灵敏度,具有更高的亲和力和更慢的解离率提高了性能. 然而,这些结合性质不能在ADA测试中可靠地预测药物耐受性.
科学领域:
- 生物制药的发展.
- 免疫性评估免疫性评估
- 测试验证的验证方法
背景情况:
- 对抗药物抗体 (ADA) 的监测对于重组蛋白疗法至关重要.
- 阳性对照对ADA试验质量控制至关重要.
- 积极对照的结合性对ADA试验性能的影响尚未完全理解.
研究的目的:
- 调查代用阳性对照的亲和力和动力参数如何影响ADA试验的性能.
- 确定阳性对照的结合特征与ADA测定灵敏度和药物耐受性之间的关系.
主要方法:
- 评估了一组具有不同结合性质的代用阳性对照组.
- 使用生物层干扰计 (BLI) 测量结合特征.
- 评估了相对敏感性和药物耐受性的ADA测定.
主要成果:
- 较高的亲和度 (较低的KD) 和较低的偏离率常数 (koff) 与相对测试灵敏度的增加相关.
- 结合参数和药物耐受性之间没有观察到一致的相关性.
- 阳性对照的结合动力学显著影响测试灵敏度,但不一定影响药物耐受性.
结论:
- 了解正控结合特性有助于选择试剂以优化ADA试验灵敏度.
- 阳性对照的选择可以显著影响测试灵敏度.
- 替代对照可能不完全代表临床ADA反应,突出了局限性.
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