文章：

靶向急性髓系白血病母细胞IL-10R的嵌合抗原受体T细胞治疗

Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells

原文发布日期：2021-08-14

DOI: 10.1038/s41408-021-00536-x

类型: Article

开放获取: 是

英文摘要：

Acute myeloid leukemia (AML) is a biologically and clinically heterogeneous disease with a dismal prognosis and limited treatment options. Chimeric antigen receptor (CAR) T cells have achieved unprecedented clinical responses in patients with B cell malignancies but a dismal consequences in AML. In our previous study, we found that interleukin-10 receptor (IL-10R) was overexpressed in most AML cells, and played an important role in promoting the stemness of leukemia cells. In this study, we developed a novel ligand-based CAR-T cell targeting IL-10R, which displayed striking cytotoxicity both in vitro and in vivo against AML cells. Except for monocytes, it had no significant adverse effects on the normal hematopoietic system, including CD34+ hematopoietic stem and progenitor cells (HSPCs). In addition, even though the incorporation of IL-10 in the CAR cassette led to phenotypes change, it had few adverse effects on the survival and biological activity of IL-10 CAR-T cells and did not cause excessive proliferation of leukemia cells. Therefore, we propose IL-10R is a novel promising therapeutic candidate for AML, and IL-10R targeted CAR-T therapy provides a new treatment strategy to improve the prognosis of AML.
 

摘要翻译： 

急性髓系白血病（AML）是一种生物学和临床异质性疾病，预后不良且治疗选择有限。嵌合抗原受体（CAR）T细胞在B细胞恶性肿瘤患者中取得了前所未有的临床疗效，但在AML中效果不佳。我们先前的研究发现，白细胞介素-10受体（IL-10R）在大多数AML细胞中过度表达，并在促进白血病细胞干性方面发挥重要作用。本研究开发了一种新型靶向IL-10R的基于配体的CAR-T细胞，其在体外和体内均对AML细胞表现出显著的细胞毒性。除单核细胞外，该疗法对包括CD34+造血干细胞和祖细胞（HSPCs）在内的正常造血系统无明显不良影响。此外，尽管CAR结构中整合了IL-10导致表型变化，但对IL-10 CAR-T细胞的存活和生物学活性影响甚微，且未引起白血病细胞过度增殖。因此，我们认为IL-10R是AML治疗中具有潜力的新型靶点，针对IL-10R的CAR-T疗法为改善AML预后提供了新的治疗策略。

原文链接：

Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells