肿瘤细胞治疗研究
英文原题：The TCR in CAR T cell therapy: use it or lose it?
The TCR in CAR T cell therapy: use it or lose it?
嵌合抗原受体（CAR）T细胞疗法已成为治疗某些血液系统恶性肿瘤不可或缺的免疫疗法，但仍面临诸多挑战，包括抗原逃逸、患者反应差异、毒性、CAR T细胞持久性有限以及高成本，尤其是在针对实体瘤时。
嵌合抗原受体 (CAR) T 细胞疗法已成为治疗某些血液系统肿瘤不可或缺的免疫疗法，但仍面临诸多挑战，包括抗原逃逸、患者反应差异、毒性、CAR T 细胞持久性有限和高成本，尤其是在针对实体瘤时。本综述讨论内源性 T 细胞受体 (TCR) 作为 CAR T 细胞功能的阻碍或伙伴的潜在作用。具体而言，我们讨论 CAR 与 TCR 在结构和功能上的差异和相似之处，支持在 CAR T 细胞中消除 TCR 价值的研究发现，以及相反地，支持在 CAR T 细胞疗法中保留和利用内源性 TCR 的数据。我们认为，虽然 TCR 敲除系统可能改善 CAR 疗法的通用性、成本和 CAR 表达等方面，但内源性 TCR 在维持 CAR T 细胞持久性方面继续发挥重要作用，并可用于增强 CAR T 细胞的治疗表型。总体而言，我们强调 CAR T 细胞疗法领域持续存在的不确定性，并概述关于 CAR T 细胞 TCR 的新兴证据和方向，这些有可能改变患者结局。
Chimeric antigen receptor (CAR) T cell therapy has become an indispensable immunotherapy for the treatment of some hematologic cancers, but still faces numerous challenges in the form of antigen escape, variable patient responses, toxicities, limited CAR T cell persistence, and high cost, particularly against solid tumors. This Review discusses the potential role of the endogenous T cell receptor (TCR) as either a hindrance or partner to CAR T cell function. Specifically, we discuss the differences and similarities between CAR and TCR structure and function, findings supporting the value of TCR elimination in CAR T cells, and, in contrast, data in support of retaining and utilizing the endogenous TCR in CAR T cell therapy. We make the case that, while TCR-knockout systems may improve aspects such as the universality, cost, and CAR expression of CAR therapies, the endogenous TCR continues to play a significant role in maintaining CAR T cell persistence and can be used to augment CAR T cell therapeutic phenotypes. Overall, we highlight the uncertainties that persist within the field of CAR T cell therapy and outline emerging evidence and directions regarding the CAR T cell TCR that have the potential to transform patient outcomes.
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