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Nature Medicine:发现可输送抗体到肿瘤的细胞入口

摘要 : 美国加州圣地亚哥蛋白组学系统医学研究所和悉尼·金梅尔癌症研究中心的研究人员发现,啮齿动物的一个细胞入口能够让抗体或其他药物从血液里输送到固体癌症肿瘤中。该发现为建立低剂量快速渗入肿瘤的新疗法和成像方案提供了新的可能。相关文章发表于2014年8月17日的《Nature Medicine》杂志上。


利用肿瘤成像和蛋白表达记录技术,Jan Schnitzer等人发现膜联蛋白annexin A1的一种裂开形式能够独一无二地集中到人类和啮齿动物的肿瘤血管的细胞膜穴样内陷中。



In vivo proteomic imaging analysis of caveolae reveals pumping system to penetrate solid tumors

Phil Oh, Jacqueline E Testa, Per Borgstrom, Halina Witkiewicz, Yan Li & Jan E Schnitzer

Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrate tumors. A post-translationally modified form of annexin A1 (AnnA1) is selectively concentrated in human and rodent tumor caveolae. To follow trafficking, we generated a specific AnnA1 antibody that targets caveolae in the tumor endothelium. Intravital microscopy of caveolae-immunotargeted fluorophores even at low intravenous doses showed rapid and robust pumping across the endothelium to enter mammary, prostate and lung tumors. Within 1 h, the fluorescence signal concentrated throughout tumors to exceed the peak levels in blood. This transvascular pumping required the expression of caveolin 1 and annexin A1. Tumor uptake with other antibodies were >100-fold less. This proteomic imaging strategy reveals a unique target, antibody and caveolae pumping system for solid tumor penetration.

来源: 中国科学报 浏览次数:148


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