解锁T细胞耗尽：洞察力和对CAR-T细胞疗法的影响
Unlocking T cell exhaustion: Insights and implications for CAR-T cell therapy
影响因子:14.60000
分区:医学1区 Top / 药学1区
发表日期:2024 Aug
作者:
Dian Xiong, Haijun Yu, Zhi-Jun Sun
摘要
嵌合抗原受体T（CAR-T）细胞疗法作为一种收养细胞疗法（ACT）的一种形式，在癌症治疗方面表现出了巨大的希望，这是由FDA批准的针对CD19或B细胞成熟抗原（BCMA）的CAR-T细胞疗法证明的，对血液学恶性肿瘤而言，对固体肿瘤的血液学恶性肿瘤中的血液学恶性肿瘤。然而，尽管取得了这些进步，但CAR-T治疗的功效通常会因T细胞耗尽而损害，这种现象阻碍了CAR-T细胞的持久性和效应子功能，从而导致CD19或CD22 CAR-T细胞治疗的患者的复发率高达75％。克服CAR-T精疲力竭的策略采用最先进的基因组工程工具和单细胞测序技术。在这篇综述中，我们对T细胞耗尽的最新机械见解及其对当前优化CAR-T细胞疗法的努力的影响提供了全面的理解。这些见解与在最近的临床试验中从基于CAR-T的产品中学到的经验教训相结合，旨在应对T细胞耗尽所带来的挑战，有可能为开发量身定制的下一代癌症治疗方法奠定了基础。
Abstract
Chimeric antigen receptor T (CAR-T) cell therapy as a form of adoptive cell therapy (ACT) has shown significant promise in cancer treatment, demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen (BCMA) for hematological malignancies, albeit with moderate outcomes in solid tumors. However, despite these advancements, the efficacy of CAR-T therapy is often compromised by T cell exhaustion, a phenomenon that impedes the persistence and effector function of CAR-T cells, leading to a relapse rate of up to 75% in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies. Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies. In this review, we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy. These insights, combined with lessons learned from benchmarking CAR-T based products in recent clinical trials, aim to address the challenges posed by T cell exhaustion, potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.