CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR T-Cells in Acute Lymphoblastic Leukemia: Current Status and Future Prospects.
CAR T-Cells in Acute Lymphoblastic Leukemia: Current Status and Future Prospects.
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目前急性淋巴细胞白血病(ALL)的治疗主要依赖化疗、类固醇和异基因干细胞移植的联合应用。然而,初次完全缓解后出现难治或复发(R/R)的比例在儿童患者中最高可达20%,成人患者中甚至可达60%。为应对R/R疾病,研究者开发了嵌合抗原受体修饰T细胞(CAR-T)疗法。迄今,美国食品药品监督管理局(FDA)已批准4种用于治疗ALL的CAR-T 细胞产品。这一新策略治疗R/R ALL已取得显著成功,但CAR-T 治疗费用高、存在诸多局限,也伴有不良反应;细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)是两种常见不良反应。此外,治疗期间也可能出现CAR-T 疗法耐药或复发。研究仍在持续推进,以克服这些局限和不良反应。本文综述CAR-T 细胞治疗ALL的应用,总结相关临床试验结果,并讨论旨在提高疗效、克服局限的未来方向。
The currently available treatment for acute lymphoblastic leukemia (ALL) is mainly dependent on the combination of chemotherapy, steroids, and allogeneic stem cell transplantation.
However, refractoriness and relapse (R/R) after initial complete remission may reach up to 20% in pediatrics. This percentage may even reach 60% in adults. To overcome R/R, a new therapeutic approach was developed using what is called chimeric antigen receptor-modified (CAR) T-cell therapy. The Food and Drug Administration (FDA) in the United States has so far approved four CAR T-cells for the treatment of ALL. Using this new therapeutic strategy has shown a remarkable success in treating R/R ALL.
However, the use of CAR T-cells is expensive, has many imitations, and is associated with some adverse effects. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are two common examples of these adverse effects.
Moreover, R/R to CAR T-cell therapy can take place during treatment. Continuous development of this therapeutic strategy is ongoing to overcome these limitations and adverse effects. The present article overviews the use of CAR T-cell in the treatment of ALL, summarizing the results of relevant clinical trials and discussing future prospects intended to improve the efficacy of this therapeutic strategy and overcome its limitations.
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