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固体瘤及其微环境的三维建模,以评估T细胞治疗在体外的有效性
Ronja Pscheid1,2, Esther Drent1, Judith Wienke2
1Gadeta B.V., Utrecht, the Netherlands.
Journal of immunology (Baltimore, Md. : 1950)
|June 9, 2023
概括
研究人员开发了一种新的3D模型,用于测试工程T细胞 (TEG A3) 对固体瘤的抗击. 这个模型有效地展示了TEG A3的TEG A3.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 固体瘤免疫疗法面临的挑战是由于不足的体外模型,无法复制瘤微环境.
- 三维 (3D) 模型对于准确评估抗瘤免疫反应至关重要.
研究的目的:
- 为了评估与马-达 (γδ) T 细胞受体 (TCR) 工程的α-β (αβ) T 细胞的抗瘤反应性,称为TEG A3.
- 建立和验证可重现的3D细胞毒性试验,用于临床前免疫疗法评估.
主要方法:
- 开发一种无血清3D细胞毒性测定方法,使用细胞系衍生球体和患者衍生瘤器官.
- 监测T细胞介导的瘤细胞溶解通过活细胞成像与亡标志物和干扰素- (IFN-γ) 分泌.
- 纳入纤维细胞,在3D模型中创建一个更复杂的瘤微环境.
主要成果:
- 3D测定成功地证明了TEG A3对表达CD277J的瘤细胞的反应性.
- 在复杂的3D模型中,TEG A3在48小时内表现出瘤特异性化细胞.
- 该试验有效模拟了异质瘤微环境,包括与纤维细胞的相互作用.
结论:
- 复杂的3D细胞毒性测试对于在临床前环境中评估基于T细胞的免疫疗法非常有价值.
- 该模型系统为早期开发和对固体瘤新型免疫疗法的功能评估提供了一个强大的平台.
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