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Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor
Molecular Cancer Therapeutics ( IF 5.3 ) Pub Date : 2020-03-03 , DOI: 10.1158/1535-7163.mct-19-0959
Sudeep Banerjee 1, 2 , Hyunho Yoon 1 , Mayra Yebra 1 , Chih-Min Tang 1 , Mara Gilardi 3 , Jayanth S Shankara Narayanan 1 , Rebekah R White 1 , Jason K Sicklick 1 , Partha Ray 1
Affiliation  

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro. Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro. The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo.

中文翻译:


用于胃肠道间质瘤靶向标记的抗 KIT DNA 适体



胃肠道间质瘤 (GIST) 是最常见的肉瘤,其特征是 KIT 蛋白过度表达,并且肿瘤常常由致癌 KIT 突变驱动。 KIT 的靶向抑制彻底改变了 GIST 治疗,并开创了治疗实体恶性肿瘤的精准医学时代。在这里,我们首次使用 KIT 特异性 DNA 适体来靶向标记 GIST。我们发现抗 KIT DNA 适体以 KIT 依赖性方式结合细胞,并且对体外 GIST 细胞标记具有高度特异性。在功能上,KIT 适体以类似于 KIT mAb 染色的方式结合细胞外 KIT,并在体外进行细胞内运输。 KIT 适体以突变不可知的方式结合分离的原代人 GIST 细胞,从而标记具有 KIT 和 PDGFRA 突变的肿瘤。此外,KIT 适体还可以高灵敏度地离体标记完整的人类 GIST 组织以及小鼠腹膜异种移植物。这些结果代表了首次使用基于适配体的方法在体外和体内靶向检测 GIST。
更新日期:2020-03-03
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