The mechanisms and countermeasures for CAR-T cell expansion and persistence deficiency

IF 9.1 1区 医学 Q1 ONCOLOGY
Yu-Tong Bao , Meng Lv , Xiao-Jun Huang , Xiang-Yu Zhao
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引用次数: 0

Abstract

Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological malignancies, particularly B-cell malignancies. However, its high risk of relapse and low efficacy in malignancies such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) have limited its clinical utility. The expansion, infiltration and persistence of CAR-T cells are key determinants of their efficacy. It has been recognized that limited expansion and lack of persistence are major contributors to non-remission and early relapse, highlighting the need to elucidate their mechanisms and countermeasures. In this review, we described features of CAR-T cell expansion and persistence in various hematogenic malignancies and solid tumors. Then, current knowledge on the mechanisms underlying deficiency in CAR-T cell expansion and persistence is presented, focusing on the intrinsic deficiency of CAR-T cells as well as their interaction with the systemic and local immune environment. Finally, we summarize approaches to enhance CAR-T cell expansion and persistence by improving CAR-T cell quality and overcoming the immunosuppressive environment.
CAR-T细胞扩增和持久性缺陷的机制及对策
嵌合抗原受体(CAR) T细胞疗法已成为血液系统恶性肿瘤,特别是b细胞恶性肿瘤的突破性治疗方法。然而,其在慢性淋巴细胞白血病(CLL)和急性髓系白血病(AML)等恶性肿瘤中的复发率高、疗效低,限制了其临床应用。CAR-T细胞的扩张、浸润和持久性是其疗效的关键决定因素。人们已经认识到,有限的扩大和缺乏持久性是导致不缓解和早期复发的主要原因,强调有必要阐明其机制和对策。在这篇综述中,我们描述了CAR-T细胞在各种血液恶性肿瘤和实体肿瘤中的扩增和持续的特征。然后,介绍了目前关于CAR-T细胞扩增和持久性缺陷机制的知识,重点介绍了CAR-T细胞的内在缺陷以及它们与全身和局部免疫环境的相互作用。最后,我们总结了通过改善CAR-T细胞质量和克服免疫抑制环境来增强CAR-T细胞扩增和持久性的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer letters
Cancer letters 医学-肿瘤学
CiteScore
17.70
自引率
2.10%
发文量
427
审稿时长
15 days
期刊介绍: Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.
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