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五种常见肿瘤膜蛋白抗原的表达谱:用于开发适用于多数实体瘤患者的鸡尾酒 CAR-T 细胞疗法

英文原题:Expression Profiles of Five Common Cancer Membrane Protein Antigens Collected for the Development of Cocktail CAR-T Cell Therapies Applicable to Most Solid Cancer Patients.

PubMed 2025/02/27(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

研究概要

尽管CD19 CAR-T对B细胞血液癌症高度有效,但关于成功治疗实体癌的报道很少,可能是因为在癌细胞膜表面特异性表达的蛋白质抗原很少。

中文摘要

尽管CD19 CAR-T对B细胞血液肿瘤高度有效,但关于成功治疗实体瘤的报道很少,这可能是因为在癌细胞膜表面特异性表达的蛋白质抗原很少。开发一种对实体瘤有效的突破性CAR-T细胞疗法的关键在于“克服癌症抗原的异质性”。为此,需要同时靶向多种癌症抗原。在本研究中,我们使用针对ROBO1、EphB4、CLDN1和LAT1的抗体,以及我们先前研究过的GPC3,对多种实体瘤标本进行了免疫组织化学分析。这些抗原在多种实体瘤中频繁表达,但除少数例外,在邻近癌症的非癌正常器官中很少表达。尽管ROBO1和GPC3常在细胞质中表达,但根据癌症类型的不同,也存在在细胞膜上表达的情况。另一方面,已揭示三种抗原——EphB4、CLDN1和LAT1——在多种实体瘤中仅在癌细胞膜上频繁表达,表明它们可能是CAR-T细胞治疗的理想靶点。

展开英文摘要原文

Although CD19 CAR-T has been highly effective against B-cell blood cancers, there are few reports of successful treatments for solid cancers, probably because there are few protein antigens specifically expressed on the surface of the cancer cell membrane. The key to developing a groundbreaking CAR-T cell therapy effective against solid cancers is to "overcome the heterogeneity of cancer antigens". For this purpose, it is necessary to target multiple cancer antigens simultaneously. In this study, we performed immunohistochemical analysis of various solid cancer specimens using antibodies against ROBO1, EphB4, CLDN1, and LAT1 in addition to GPC3, which we have previously studied. These antigens were frequently expressed in various solid cancers but shown to be rarely expressed, with some exceptions, in non-cancerous normal organs adjacent to the cancer. Although ROBO1 and GPC3 are often expressed in cytoplasm, there are also cases in which they are expressed on the cell membrane depending on the type of cancer. On the other hand, it has been revealed that three antigens-EphB4, CLDN1, and LAT1-are frequently expressed only on the cell membrane of cancer cells in various solid cancers, suggesting that they may be ideal targets for CAR-T cell therapy.

论文信息

作者
Nakatsura T、Takenouchi K、Kataoka J、Ito Y、Kikuchi S、Kinoshita H、Ohnuki K、Suzuki T
单位
Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan.Japan
期刊
International journal of molecular sciences2025 Feb 27
原文标识
PubMed 40076777 · DOI 10.3390/ijms26052145