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靶向间皮素的免疫治疗在急性髓系白血病中的应用

英文原题:Immunotherapy targeting mesothelin in acute myeloid leukemia.

PubMed 2022/08/10(内容时间) J Leukoc Biol Q2 · IF 3.4(JCR 2025)

研究概要

有趣的是,近期研究表明MSLN在36%的急性髓系白血病(AML)患者中高表达,而在正常造血细胞中几乎不表达,这使得MSLN成为治疗AML的一个有前景的靶点。

中文摘要

间皮素(MSLN)是一个新兴靶点,存在可溶性和膜结合两种形式。它通常用于MSLN阳性实体瘤的诊断和治疗。有趣的是,近期研究表明MSLN在36%的急性髓系白血病(AML)患者中高表达,而在正常造血细胞中几乎不表达,这使得MSLN成为治疗AML的一个有前景的靶点。已有研究表明,可溶性MSLN可作为诊断标志物被检测到。尽管作用机制尚不清楚,MSLN仍然是免疫治疗的一个有前景的靶点。大多数MSLN研究是在实体瘤中进行的,在造血系统肿瘤中的研究较少。在AML这一造血系统肿瘤中,越来越多的MSLN研究正在进行。例如,MSLN与AML患者的髓外疾病、微小残留病和复发相关。降低MSLN的表达可减轻疾病病程的严重程度。这些信息表明,MSLN可能是治疗许多AML相关疾病的理想靶点,以改善预后和生存率。目前,针对AML中MSLN的免疫治疗在临床前和临床试验中有少量开展,如抗体药物偶联物、双特异性T细胞衔接器和CAR-T 细胞,这为MSLN相关AML的治疗开辟了新的空间。

展开英文摘要原文

Mesothelin (MSLN) is an emerging target that exists in soluble and membrane-associated forms. It is usually used for the diagnosis and treatment of MSLN-positive solid tumors. Interestingly, recent studies have shown that MSLN is highly expressed in 36% of acute myeloid leukemia (AML) patients and barely expressed in normal hematopoietic cells, which makes MSLN a promising target for the treatment of AML. It has been shown that MSLN is detectable as a diagnostic marker in its soluble form. Although the mechanism of action is unclear, MSLN remains a promising target for immunotherapy. Most MSLN research has been conducted in solid tumors, and less research has been conducted in hematopoietic tumors. Increasing research on MSLN is underway in AML, a hematopoietic neoplasm. For example, MSLN is related to extramedullary disease, minimal residual disease, and relapse in AML patients. Decreasing the expression of MSLN reduces the severity of the disease course. This information suggests that MSLN may be an ideal target for the treatment of many AML-related diseases to improve the prognosis and survival rate. At present, there are a few immunotherapies targeting MSLN in AML in preclinical and clinical trials, such as antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor-T cells, which opens new room for the treatment of MSLN-related AML.

论文信息

作者
Wang Q、Gong R
单位
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.China
文献类型
综述 · 非美国政府资助研究
期刊
Journal of leukocyte biology2022 Oct
原文标识
PubMed 35946307 · DOI 10.1002/JLB.5MR0622-483R