Mueller Katherine P, Grenier Jeremy M, Weber Evan W
Department of Pediatrics, Division of Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Pediatrics, Division of Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trends Cancer. 2025 Oct;11(10):1005-1018. doi: 10.1016/j.trecan.2025.08.014. Epub 2025 Sep 18.
Chimeric antigen receptor T cell (CAR T) therapies are 'living drugs' in which T cells are genetically engineered to recognize and kill cancer cells. A major barrier to progress for CAR T targeting liquid and solid tumors is the poor persistence of these cells in vivo, which limits therapeutic efficacy. In this review, we summarize the field's current understanding of CAR T persistence, including clinical observations, patient correlatives and multiomics approaches, and emerging cell engineering and manufacturing strategies. We also propose a conceptual framework for CAR T persistence to guide interpretation of clinical data and the design of more potent and efficacious CAR T therapeutics.
嵌合抗原受体T细胞（CAR T）疗法是一种“活体药物”，其中T细胞经过基因工程改造以识别并杀死癌细胞。CAR T靶向液体和实体瘤进展的一个主要障碍是这些细胞在体内的持久性较差，这限制了治疗效果。在本综述中，我们总结了该领域目前对CAR T持久性的理解，包括临床观察、患者相关性研究和多组学方法，以及新兴的细胞工程和制造策略。我们还提出了一个CAR T持久性的概念框架，以指导临床数据的解读以及更有效和高效的CAR T疗法的设计。
