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人类起源的治疗抗体的免疫性与V基因使用有关

Zicheng Hu¹, Sivan Cohen¹, Steven J Swanson¹

¹Department of BioAnalytical Sciences, Genentech Inc, South San Francisco, CA, United States.

Frontiers in immunology

|September 18, 2023

概括

治疗性抗体可以引起免疫反应,导致抗药抗体 (ADA). 这项研究发现,更多的突变和抗体序列中的罕见V等位基因增加了ADA风险,影响了药物的有效性和安全性.

科学领域:

免疫学免疫学免疫学
生物技术是生物技术.
药理学药理学是指药理学的学科.

背景情况:

治疗性抗体可以触发免疫反应,产生影响药物功能的抗药抗体 (ADA).
抗体序列多样性源于VDJ重组和突变发生,可能产生免疫性序列.

研究的目的:

为了研究VDJ重组和突变发生对临床抗药抗体 (ADA) 率的影响.
为了确定与序列相关的因素,有助于治疗抗体免疫性.

主要方法:

临床ADA率与抗体序列突变数量之间的相关性分析.
评估使用罕见V等位基因与免疫性风险之间的关联.

主要成果:

在临床ADA率和抗体序列中引入突变的数量之间观察到正相关性.
在人源抗体治疗中利用罕见的V基因组与免疫性风险增加有关.

结论:

抗体工程策略应优先考虑具有共同V等位基因的框架.
选择具有较少突变的抗体候选者可以减轻免疫性风险.

关键词:

在VDJ重组的过程中,抗药抗体 (ADA) 是一种抗药性抗体.抗体工程是针对抗体的工程.免疫性免疫性免疫性治疗性抗体治疗性抗体.

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