Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid mali...

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Veröffentlicht in:Molecular cancer therapeutics 2020-05, Vol.19 (5), p.1173-1182
Hauptverfasser: Banerjee, Sudeep, Yoon, Hyunho, Yebra, Mayra, Tang, Chih-Min, Gilardi, Mara, Shankara Narayanan, Jayanth S, White, Rebekah R, Sicklick, Jason K, Ray, Partha
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Sprache:eng
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Zusammenfassung:Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic 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 Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with and mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue , 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 and .
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-19-0959