一种简化的功能优先方法,用于发现和优化双特异性免疫参与抗体
Alex Shepherd1,2, Bigitha Bennychen1,2, Anne Marcil1
1Human Health Therapeutics Research Centre, National Research Council, Ottawa, Canada.
PloS one
|June 22, 2023
概括
这项研究引入了一种更快,更便宜的方法来开发新的双特异性T细胞参与抗体 (BiTEs). 新型BiTE-J系统允许在不经净化的情况下快速选BiTE分子,加速癌症治疗的发展.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 在瘤学瘤学.
背景情况:
- 双特异性T细胞参与抗体 (BiTEs) 是一种工程蛋白质,用于向癌症治疗的T细胞和瘤细胞.
- 目前的BiTE开发是漫长而昂贵的,涉及广泛的表征,生产和净化步骤.
- 需要更有效的方法来发现和验证新的BiTE构造.
研究的目的:
- 开发一种具有成本效益和高通量方法,用于生成和选新的BiTE序列.
- 建立一个功能优先选系统,绕过蛋白质净化需求.
- 为了识别具有增强抗瘤活性的新型BiTE分子.
主要方法:
- 一个双模块化等离子体系统被设计为快速,高通量交换抗体结合域 (scFvs).
- 开发了两种基于Jurkat T细胞的查系统 (BiTE-J),用于在不进行净化的情况下进行功能评估.
- 该系统通过选EGFRvIII向BTE和新型CD3向域来验证.
主要成果:
- 该BiTE-J系统能够快速选新的瘤向scFvs与CD3向域相结合.
- 两种新型EGFRvIII-scFvs在重定向T细胞对抗EGFRvIII表达瘤细胞方面表现出优异的活性.
- 在初级T细胞中证实了活性,显示了抗原选择性瘤杀死和T细胞激活.
结论:
- BiTE-J平台提供了一种低成本,高通量方法,用于快速评估BiTE分子.
- 这种方法大大减少了与新型BiTE开发相关的时间和成本.
- 功能优先查加速了针对各种癌症的强效BiTE治疗方法的发现.
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