对全长抗体,片段和双特异格式的开发能力的比较研究显示,工程结构的稳定性风险更高
Itzel Condado-Morales1,2, Fabian Dingfelder1,2, Isabel Waibel2
1Department of Biophysics and Injectable Formulation, Global Research Technologies, Novo Nordisk A/S, Måløv, Denmark.
mAbs
|October 4, 2024
概括
工程抗体格式显示出潜力,但面临着可开发性挑战. 全长抗体通常比复杂的工程格式,如双特异和抗体碎片,具有更高的开发能力.
科学领域:
- 生物制药的发展.
- 蛋白质工程是一种蛋白质工程.
- 免疫学 免疫学 免疫学
背景情况:
- 工程抗体格式比传统单克隆抗体 (mAbs) 有潜在的治疗优势.
- 可开发性挑战可能会阻碍新型抗体格式的临床转化.
- 瘤坏死因子 (TNF) 是各种炎症性疾病的关键点.
研究的目的:
- 系统地比较针对TNF的各种工程抗体格式的开发能力.
- 为治疗开发确定具有优越生物物理性质的特定分子格式.
- 评估与不同抗体结构的制造,稳定性和活性相关的风险.
主要方法:
- 分析了8个分子格式家族的64种抗体结构,包括全长的mAbs,单链可变片段 (scFvs) 和双特异性抗体.
- 测量15个与活动,制造和稳定性相关的生物物理性质.
- 使用基于旗的风险方法和in silico开发能力概况器对变体进行评分.
主要成果:
- 全长抗体表现出最高的整体发育能力.
- 双特异性抗体和scFvs表现出中间的发育能力.
- 复杂的格式,如diabodies和某些双特异构造,显示出对碎片化和聚合的倾向增加.
结论:
- 自然的全长抗体格式通常具有优越的可开发性配置文件.
- 工程抗体格式,特别是复杂的,存在重大发展障碍,包括聚合和碎片化.
- 对抗体格式的战略选择对于成功的生物制药开发至关重要.
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