嵌合式抗原受体中的4-1BBζ共刺激域在T细胞受体刺激后增强CD8+T细胞功能
Gerard J Chu1,2,3, Charles G Bailey1,3,4, Rajini Nagarajah1
1Gene and Stem Cell Therapy Program Centenary Institute, Camperdown, NSW, Australia.
Cancer cell international
|December 17, 2023
概括
4-1BBζ 仿真抗原受体 (CAR) T 细胞增强 T 细胞受体 (TCR) 功能,改善细胞增殖和细胞因子的产生. 这种增强可能有利于癌症免疫疗法,但如果TCR针对自我抗原,则会带来风险.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 癌症研究 癌症研究
背景情况:
- 化学抗原受体 (CAR) T细胞对CD19+和BCMA+血液性恶性瘤有效.
- 关于CAR结构对T细胞受体 (TCR) 中介功能的影响仍然不完全理解.
研究的目的:
- 系统地评估CAR T细胞中的TCR信号和功能.
- 研究不同CAR共刺激性内域 (CD28与4-1BB) 对T细胞反应的影响.
主要方法:
- 产生了具有CD28或4-1BB共刺激域的人类抗美索林CAR T细胞.
- 通过使用葡萄球菌肠毒素B诱导TCR刺激.
- 实验室功能测试,包括流细胞计,用于评估T细胞反应.
主要成果:
- 与对照细胞相比,CD8+ 4-1BBζ CAR T细胞的增殖,CD69表达和IFNγ产生增加了.
- 增强的TCR介导功能与酸化ZAP70水平升高相关.
- CD8+ 4-1BBζ CAR T细胞产品显示中央记忆细胞增加了两倍.
结论:
- 4-1BBζ CAR结构显著增强了CD8+ T细胞受体介导的功能.
- 这种增强可能有利于向恶性组织或病原体.
- 相反,如果TCR针对自身抗原,则可能会有害,因此需要仔细设计.
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