期刊
PHARMACEUTICALS
卷 15, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/ph15060697
关键词
immune checkpoint; PD-L1; aptamer; imaging; cancer
资金
- National Science Centre, Poland [UMO2017/25/B/NZ1/00827]
- Norwegian Research Council [296129, 311544]
- European Union under the European Regional Development Fund [POIR.04.04.00-00-420F/17-00]
- National Science Centre [2018/02/X/NZ1/02015, 2019/34/H/NZ1/00674]
- Broegelmann Foundation
- NCBiR NOR/SGS [0141/2020-00 Aptaquest]
- Western Norwegian Health Region (Helse Vest) open project [F-11216 (912167)]
- Marie Sklodowska-Curie Grant [675555]
- National Science Center [2020/37/B/NZ7/04157]
- European Regional Development Fund [POIG.02.01.00-12167/08]
- Marie Curie Actions (MSCA) [675555] Funding Source: Marie Curie Actions (MSCA)
In this study, a molecular probe based on aptamer was developed, which specifically recognizes human PD-L1. The probe showed excellent potential in cancer imaging in both in vitro and in vivo experiments.
Immune checkpoint targeting immunotherapy has revolutionized the treatment of certain cancers in the recent years. Determination of the status of immune checkpoint expression in particular cancers may assist decision making. Here, we describe the development of a single-stranded aptamer-based molecular probe specifically recognizing human PD-L1. Target engaging aptamers are selected by iterative enrichment from a random ssDNA pool and the binding is characterized biochemically. Specificity and dose dependence is demonstrated in vitro in the cell culture using human kidney tumor cells (786-0), human melanoma cells (WM115 and WM266.4) and human glioblastoma LN18 cancer cells. The utility of the probe in vivo is demonstrated using two mouse tumor models, where we show that the probe exhibits excellent potential in imaging. We postulate that further development of the probe may allow universal imaging of different types of tumors depending on their PD-L1 status, which may find utility in cancer diagnosis.
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