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工程T细胞受体融合蛋白使用非病毒CRISPR/Cas9基因组编辑用于癌症免疫治疗

Runzhe Shu^1,2, Maree Hammett^1,2, Vera Evtimov^1,2

¹Cartherics Pty Ltd. Notting Hill Australia.

Bioengineering & translational medicine

|November 29, 2023

概括

研究人员开发了一种非病毒CRISPR/Cas9方法,用于创建用于癌症免疫治疗的融合蛋白 (FP) T细胞. 这种方法为传统的仿真抗原受体 (CAR) -T细胞疗法提供了更安全,更一致的替代方案.

科学领域:

免疫学免疫学免疫学
基因编辑基因编辑
癌症治疗癌症治疗

背景情况:

化学抗原受体 (CAR) -T细胞疗法制造通常使用病毒载体,这些载体昂贵,并带有随机基因整合,变量表达,基因沉默和瘤转化等风险.
现有的CAR-T细胞生产方法在成本,安全性和一致性方面存在重大挑战.

研究的目的:

开发和优化一种非病毒,基于CRISPR/Cas9的方法,用于生成具有工程瘤向受体的T细胞.
通过将抗瘤单链可变片段 (scFvs) 集成到T细胞受体综合体的CD3ε子单元中,创建融合蛋白 (FP) T细胞.

主要方法:

利用CRISPR/Cas9基因组编辑与大型捐赠者DNA,将抗瘤scFv敲入CD3ε的N端.
生成的融合蛋白 (FP) T细胞,将工程受体集成到TCR/CD3复合体中.
通过将scFvs结合到其他CD3子单元和CD28中,开发出双向FPT细胞.

主要成果:

与传统的CAR-T细胞相比,实现了具有较低基因表达变异性的CD3εFPT细胞的高效生成.
证明了良好的细胞扩张和占主导地位的CD8+效应因子记忆T细胞种群.
在体外和体内确认了工程T细胞的抗瘤活性.

结论:

非病毒CRISPR/Cas9方法为产生具有瘤向受体的T细胞提供了多功能和高效的替代方案.
这种方法比病毒方法具有潜在的优势,包括提高癌症免疫治疗的安全性和一致性.
生成的FPT细胞显示出治疗癌症的有希望的治疗潜力.

关键词:

卡特 - 卡特 - 卡特 - 卡特这就是CRISPR/Cas9的作用.融合蛋白质是融合蛋白质的组成部分.免疫疗法免疫疗法非病毒性非病毒性.

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