期刊
MOLECULAR CANCER THERAPEUTICS
卷 19, 期 5, 页码 1173-1182出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-19-0959
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资金
- Surgical Society of the Alimentary Tract Mentored Research Award
- NIH [T32 CA121938, K08 CA168999, R01 CA226803, S10OD021831]
- Hope for a Cure Foundation
- The Life Raft Group
- Kristen Ann Carr Fund
- Lighting the Path Forward for GIST Cancer Research
- David Foundation
- FDA [R01 FD006334]
- UC San Diego Health Sciences Research Grant
- CCSG Grant [P30CA23100]
- UCSD Specialized Cancer Center Support Grant [(NCI) P30 2P30CA023100-28]
- UCSD Academic Senate Health Sciences Research Grant
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.
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