CD2共刺激桥梁强大的CAR诱导细胞解和持久的持久性
Fang Liu1, John T Keane1, Hyeon S Lewis1
1Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Journal for immunotherapy of cancer
|January 22, 2026
概括
新的CD2z CAR T细胞疗法将快速瘤减少与持续的T细胞持久性相结合,为癌症治疗提供了与当前的CD28和4-1BB辅助刺激领域的有希望的替代方案.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 细胞疗法细胞疗法
背景情况:
- 目前的CAR T细胞疗法利用CD28或4-1BB共刺激域,这通常有利于快速细胞杀死或长期持久性,但很少有这两种.
- 之前的研究表明,CD2-CD58参与改善了CAR T细胞的反应,但CD2细胞内信号传递的具体作用尚不清楚.
研究的目的:
- 研究CD2细胞质尾部 (CD2z) 作为CAR T细胞中共刺激域的疗效.
- 在临床前模型中,将CD2z CAR T细胞与传统的CD28 (28z) 和4-1BB (BBz) CAR T细胞进行比较.
主要方法:
- 具有CD2z,28z或BBz共刺激域的工程抗美索林和抗TnMUC1CAR T细胞.
- 用暂时mRNA表达来评估T细胞功能,用于流量和脱粒化,以及用lentiviral CARs进行持久测定.
- 在体外和NSG异种移植模型中评估了细胞因子释放,基因表达和抗瘤活性.
主要成果:
- 与28z和BBz相比,CD2zCAR T细胞表现出高效的脱粒和中间流.
- 在体内研究表明,CD2z CAR T细胞在间皮瘤和胰腺癌模型中诱导了持久的瘤回归.
- CD2z CAR T细胞表现出与28z相比的瘤控制和比BBz更好的早期瘤清除,持续的外周T细胞持久性.
结论:
- CD2细胞质尾部提供平衡的辅助刺激,实现了强大的瘤解体和T细胞持久性.
- 在下一代CAR T细胞疗法中,CD2z代表了对CD28和4-1BB共刺激域的多功能且潜在优越的替代方案.
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