Homogeneous, Low‐volume, Efficient, and Sensitive Quantitation of Circulating Exosomal PD‐L1 for Cancer Diagnosis and Immunotherapy Response Prediction. Issue 12 (31st January 2020)

• Record Type: Journal Article
• Authors: Huang, Mengjiao; Yang, Juanjuan; Wang, Teng; Song, Jia; Xia, Jinglu; Wu, Lingling; Wang, Wei; Wu, Qiaoyi; Zhu, Zhi; Song, Yanling; Yang, Chaoyong
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 12(2020)
• Page Start: 4800
• Page End: 4805
• Publication Date: 2020-01-31
• Subjects: aptamers -- exosomes -- liquid biopsy -- PD-L1 -- thermophoresis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201916039
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Immunotherapy has revolutionized cancer treatment, but its efficacy is severely hindered by the lack of effective predictors. Herein, we developed a homogeneous, low‐volume, efficient, and sensitive exosomal programmed death‐ligand 1 (PD‐L1, a type of transmembrane protein) quantitation method for cancer diagnosis and immunotherapy response prediction (HOLMES‐ExoPD‐L1 ). The method combines a newly evolved aptamer that efficiently binds to PD‐L1 with less hindrance by antigen glycosylation than antibody, and homogeneous thermophoresis with a rapid binding kinetic. As a result, HOLMES‐ExoPD‐L1 is higher in sensitivity, more rapid in reaction time, and easier to operate than existing enzyme‐linked immunosorbent assay (ELISA)‐based methods. As a consequence of an outstanding improvement of sensitivity, the level of circulating exosomal PD‐L1 detected by HOLMES‐ExoPD‐L1 can effectively distinguish cancer patients from healthy volunteers, and for the first time was found to correlate positively with the metastasis of adenocarcinoma. Overall, HOLMES‐ExoPD‐L1 brings a fresh approach to exosomal PD‐L1 quantitation, offering unprecedented potential for early cancer diagnosis and immunotherapy response prediction. Abstract : An aptamer‐induced thermophoresis quantitation of exosomal programmed death‐ligand 1 (PD‐L1, a transmembrane protein) was developed, which integrates effective recognition of aptamer and homogeneous thermophoresis. The facile technique is more sensitive and efficient than the current enzyme‐linked immunosorbent assay (ELISA)‐based methods. Translation of the method into standard clinical practice for immunotherapy prediction and monitoring is anticipated.