Imaging of Clear Cell Renal Carcinoma with Immune Checkpoint Targeting Aptamer-Based Probe

利用免疫检查点靶向适体探针对透明细胞肾癌进行成像

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作者:Stanisław Malicki, Barbara Pucelik, Edyta Żyła, Małgorzata Benedyk-Machaczka, Wojciech Gałan, Anna Golda, Alicja Sochaj-Gregorczyk, Marta Kamińska, João Crispim Encarnação, Barbara Chruścicka, Hans-Peter Marti, Tony Jialiang Chen, Katarzyna Magiera-Mularz, Bartosz Zięba, Tad A Holak, Janusz M Dąbrow

Abstract

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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