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CD33白血病干细胞和嵌合抗原受体T细胞(CAR-T细胞)作为急性髓系白血病治疗中有趣的靶点的总体情况。

A general view of CD33 leukemic stem cells and CAR-T cells as interesting targets in acute myeloblatsic leukemia therapy.

作者信息

Fathi Ezzatollah, Farahzadi Raheleh, Sheervalilou Roghayeh, Sanaat Zohreh, Vietor Ilja

机构信息

Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Blood Res. 2020 Mar;55(1):10-16. doi: 10.5045/br.2020.55.1.10. Epub 2020 Mar 30.

Abstract

Acute myeloblastic leukemia (AML) is the most frequent acute leukemia in adulthood with very poor overall survival rates. In the past few decades, significant progresses had led to the findings of new therapeutic approaches and the better understanding of the molecular complexity of this hematologic malignancy. Leukemic stem cells (LSCs) play a key role in the initiation, progression, regression, and drug resistance of different types of leukemia. The cellular and molecular characteristics of LSCs and their mechanism in the development of leukemia had not yet been specified. Therefore, determining their cellular and molecular characteristics and creating new approaches for targeted therapy of LSCs is crucial for the future of leukemia research. For this reason, the recognition of surface maker targets on the cell surface of LSCs has attracted much attention. CD33 has been detected on blasts in most AML patients, making them an interesting target for AML therapy. Genetic engineering of T cells with chimeric antigen receptor (CAR-T cell therapy) is a novel therapeutic strategy. It extends the range of antigens available for use in adoptive T-cell immunotherapy. This review will focus on CAR-T cell approaches as well as monoclonal antibody (mAB)-based therapy, the two antibody-based therapies utilized in AML treatment.

摘要

急性髓系白血病(AML)是成人中最常见的急性白血病,总体生存率极低。在过去几十年中,重大进展带来了新治疗方法的发现,并加深了对这种血液系统恶性肿瘤分子复杂性的理解。白血病干细胞(LSCs)在不同类型白血病的起始、进展、消退和耐药中起关键作用。LSCs的细胞和分子特征及其在白血病发生发展中的机制尚未明确。因此,确定其细胞和分子特征并开发针对LSCs的新靶向治疗方法对白血病研究的未来至关重要。出于这个原因,识别LSCs细胞表面的表面标志物靶点备受关注。在大多数AML患者的原始细胞上已检测到CD33,使其成为AML治疗的一个有吸引力的靶点。用嵌合抗原受体对T细胞进行基因工程改造(CAR-T细胞疗法)是一种新型治疗策略。它扩展了可用于过继性T细胞免疫疗法的抗原范围。本综述将聚焦于CAR-T细胞方法以及基于单克隆抗体(mAB)的疗法,这两种基于抗体的疗法用于AML治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e5/7106116/772e1d5fb451/br-55-10-g001.jpg

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