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间皮素:超越实体瘤的免疫治疗靶点

英文原题:Mesothelin: An Immunotherapeutic Target beyond Solid Tumors.

PubMed 2022/03/18(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

现代靶向癌症治疗依赖于肿瘤相关抗原的过表达,而这些抗原在正常细胞类型中表达极少甚至不表达。

中文摘要

现代靶向癌症治疗依赖于肿瘤相关抗原的过表达,而这些抗原在正常细胞类型中表达极少甚至不表达。间皮素是一种糖基磷脂酰肌醇锚定的细胞表面蛋白,已在多种不同类型的肿瘤中被发现,包括肺腺癌、卵巢癌,以及最近在血液系统恶性肿瘤中,包括急性髓系白血病(AML)。尽管间皮素的功能在很大程度上仍不明确,但其与 MUC16/CA125 的相互作用表明,间皮素在增殖、生长和黏附信号的调控中发挥作用。目前大多数关于间皮素的研究集中于利用间皮素设计靶向癌症疗法,如单克隆抗体、抗体-药物偶联物、CAR-T 细胞和 NK 细胞、双特异性 T 细胞衔接分子以及靶向 α 疗法等。在间皮素阳性 AML 模型中使用不同免疫治疗方式进行的体外和体内研究,均凸显了该方法作为一种治疗难以治愈的 AML 的独特机会所具有的潜在影响。

展开英文摘要原文

Modern targeted cancer therapies rely on the overexpression of tumor associated antigens with very little to no expression in normal cell types. Mesothelin is a glycosylphosphatidylinositol-anchored cell surface protein that has been identified in many different tumor types, including lung adenocarcinomas, ovarian carcinomas, and most recently in hematological malignancies, including acute myeloid leukemia (AML). Although the function of mesothelin is widely unknown, interactions with MUC16/CA125 indicate that mesothelin plays a role in the regulation of proliferation, growth, and adhesion signaling. Most research on mesothelin currently focuses on utilizing mesothelin to design targeted cancer therapies such as monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T and NK cells, bispecific T cell engaging molecules, and targeted alpha therapies, amongst others. Both in vitro and in vivo studies using different immunotherapeutic modalities in mesothelin-positive AML models highlight the potential impact of this approach as a unique opportunity to treat hard-to-cure AML.

论文信息

作者
Faust JR、Hamill D、Kolb EA、Gopalakrishnapillai A、Barwe SP
单位
Nemours Centers for Childhood Cancer Research & Cancer and Blood Disorders, Nemours Children's Hospital, Wilmington, DE 19803, USA.United States
文献类型
综述
期刊
Cancers2022 Mar 18
原文标识
PubMed 35326701 · DOI 10.3390/cancers14061550