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使用iCasp9的自杀策略来控制基因组编辑的B细胞的生长和功能,这些B细胞具有重定向的抗原特异性

Jenny Léonard¹, Marine Cahen¹, Anne-Laure Tanguy¹

¹INSERM UMR1236, University of Rennes, Etablissement Français du sang, 35000 Rennes, France.

Molecular therapy. Oncology

|December 24, 2025

概括

基因组编辑可以为免疫疗法设计B细胞,但需要采取安全措施. 这项研究引入了可诱导的caspase-9 (iCasp9) 自杀基因系统用于B细胞疗法,可控制细胞死亡和调节治疗分子输液.

科学领域:

免疫学免疫学免疫学
细胞疗法细胞疗法
基因工程是一种基因工程.

背景情况:

B细胞对免疫疗法有希望,但缺乏综合安全策略.
恶性转变是B细胞疗法的一个问题.
现有的B细胞基因组编辑方法不包含安全开关.

研究的目的:

评估B细胞中可诱导的caspase-9 (iCasp9) 自杀基因的疗效.
为工程B细胞免疫疗法制定安全策略.
评估B细胞功能和治疗分子表达的调制.

主要方法:

通过将iCasp9自杀基因和瘤抗原特异性单链免疫球蛋白录音带插入IgH位点来改造B细胞.
在瘤模型中使用药物AP1903在体外和体内激活了iCasp9.
在治疗后评估B细胞亡,功能和抵抗机制.

主要成果:

一次基因组编辑使iCasp9和抗原特异性抗体的共同表达成为可能,从而保留了B细胞的功能.
AP1903治疗在体外和体外的编辑B细胞中有效诱导了亡.
AP1903治疗导致了具有降低iCasp9和治疗盒表达的耐药细胞的选择.

结论:

该iCasp9/AP1903系统作为一个高效的安全开关工程B细胞免疫疗法.
这个系统可以作为一种新辅助疗法和一种修静剂来控制治疗分子的输送.
需要进行进一步的研究,以克服采用免疫疗法协议中的抗性机制.

关键词:

B细胞是B细胞的组成部分.MT: 定期发行定期发行收养免疫疗法采用免疫疗法.工程B细胞的工程B细胞.基因组编辑基因组编辑自杀基因自杀基因

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