Lixia Wang, Gang Jin, Qiuping Zhou, Yanyan Liu, Xiaocui Zhao, Zhuoyang Li, Na Yin, Min Peng
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引用次数: 0
摘要
嵌合抗原受体(CAR)T细胞的长期抗肿瘤疗效取决于其在体内的功能持久性。具有干细胞特性的T细胞具有更好的持久性,但赋予T细胞真正干细胞特性的因素仍有待确定。在这里,我们展示了诱导CAR T细胞进入不死样和功能性状态(称为TIF)的方法。CARTIF细胞的诱导取决于两个因子BCOR和ZC3H12A的抑制,并且需要抗原或CAR补体信号。重编程的CARTIF细胞几乎具有无限干性,类似于诱导多能干细胞,同时保留了成熟T细胞的功能,因而具有卓越的抗肿瘤效果。消除靶细胞后,CARTIF 细胞进入新陈代谢休眠状态,在体内以饱和龛位持续存在,并提供记忆保护。TIF 代表了一种具有空前干性的新型 T 细胞状态,它赋予了 CAR T 细胞在体内长期存在的功能,在 T 细胞疗法中具有广泛的潜力。
Induction of immortal-like and functional CAR T cells by defined factors.
Long-term antitumor efficacy of chimeric antigen receptor (CAR) T cells depends on their functional persistence in vivo. T cells with stem-like properties show better persistence, but factors conferring bona fide stemness to T cells remain to be determined. Here, we demonstrate the induction of CAR T cells into an immortal-like and functional state, termed TIF. The induction of CARTIF cells depends on the repression of two factors, BCOR and ZC3H12A, and requires antigen or CAR tonic signaling. Reprogrammed CARTIF cells possess almost infinite stemness, similar to induced pluripotent stem cells while retaining the functionality of mature T cells, resulting in superior antitumor effects. Following the elimination of target cells, CARTIF cells enter a metabolically dormant state, persisting in vivo with a saturable niche and providing memory protection. TIF represents a novel state of T cells with unprecedented stemness, which confers long-term functional persistence of CAR T cells in vivo and holds broad potential in T cell therapies.
期刊介绍:
Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
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