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引用次数: 0
摘要
嵌合抗原受体 T(CAR-T)细胞疗法作为一种领养细胞疗法(ACT),在癌症治疗中显示出了巨大的前景,美国食品及药物管理局批准的以 CD19 或 B 细胞成熟抗原(BCMA)为靶点的 CAR-T 细胞疗法治疗血液恶性肿瘤就证明了这一点,尽管这种疗法在实体瘤中的疗效一般。然而,尽管取得了这些进展,CAR-T疗法的疗效却常常因T细胞衰竭而大打折扣,这种现象阻碍了CAR-T细胞的持久性和效应功能,导致使用CD19或CD22 CAR-T细胞治疗血液恶性肿瘤的患者复发率高达75%。克服 CAR-T 衰竭的策略采用了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,我们将全面介绍 T 细胞衰竭的最新机理及其对当前优化 CAR-T 细胞疗法的影响。这些见解与近期临床试验中基于 CAR-T 产品的基准测试所获得的经验教训相结合,旨在解决 T 细胞衰竭带来的挑战,为开发量身定制的下一代癌症治疗方法奠定基础。
Unlocking T cell exhaustion: Insights and implications for CAR-T cell therapy
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.
Acta Pharmaceutica Sinica. BPharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
22.40
自引率
5.50%
发文量
1051
审稿时长
19 weeks
期刊介绍:
The Journal of the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association oversees the peer review process for Acta Pharmaceutica Sinica. B (APSB).
Published monthly in English, APSB is dedicated to disseminating significant original research articles, rapid communications, and high-quality reviews that highlight recent advances across various pharmaceutical sciences domains. These encompass pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis, and pharmacokinetics.
A part of the Acta Pharmaceutica Sinica series, established in 1953 and indexed in prominent databases like Chemical Abstracts, Index Medicus, SciFinder Scholar, Biological Abstracts, International Pharmaceutical Abstracts, Cambridge Scientific Abstracts, and Current Bibliography on Science and Technology, APSB is sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association. Its production and hosting are facilitated by Elsevier B.V. This collaborative effort ensures APSB's commitment to delivering valuable contributions to the pharmaceutical sciences community.