Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor
| Autor: | Jayanth S. Shankara Narayanan, Hyunho Yoon, Rebekah R. White, Mayra Yebra, Sudeep Banerjee, Partha Ray, Jason K. Sicklick, Chih-Min Tang, Mara Gilardi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Gastrointestinal Stromal Tumors medicine.drug_class Aptamer Mice Nude Apoptosis PDGFRA Monoclonal antibody Article Mice 03 medical and health sciences 0302 clinical medicine In vivo Tumor Cells Cultured medicine Animals Humans Stromal tumor neoplasms Cell Proliferation Gastrointestinal Neoplasms GiST Chemistry Antibodies Monoclonal Aptamers Nucleotide Xenograft Model Antitumor Assays digestive system diseases In vitro Proto-Oncogene Proteins c-kit 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Female Ex vivo |
| Zdroj: | Mol Cancer Ther |
| ISSN: | 1538-8514 1535-7163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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