Campbell, E. orcid.org/0000-0001-9564-9408, Adamson, H. orcid.org/0000-0002-2582-3287, Kohl, D. et al. (4 more authors) (Cover date: 1 October 2023) Enzyme - Switch sensors for therapeutic drug monitoring of immunotherapies. Biosensors and Bioelectronics, 237. 115488. ISSN 0956-5663
Abstract
Therapeutic monoclonal antibodies (TmAb) have emerged as effective treatments for a number of cancers and autoimmune diseases. However, large interpatient disparities in the pharmacokinetics of TmAb treatment requires close therapeutic drug monitoring (TDM) to optimise dosage for individual patients. Here we demonstrate an approach for achieving rapid, sensitive quantification of two monoclonal antibody therapies using a previously described enzyme switch sensor platform. The enzyme switch sensor consists of a β-lactamase - β-lactamase inhibitor protein (BLA-BLIP) complex with two anti-idiotype binding proteins (Affimer proteins) as recognition elements. The BLA-BLIP sensor was engineered to detect two TmAbs (trastuzumab and ipilimumab) by developing constructs incorporating novel synthetic binding reagents to each of these mAbs. Trastuzumab and ipilimumab were successfully monitored with sub nM sensitivity in up to 1% serum, thus covering the relevant therapeutic range. Despite the modular design, the BLA-BLIP sensor was unsuccessful in detecting two further TmAbs (rituximab and adalimumab), an explanation for which was explored. In conclusion, the BLA-BLIP sensors provide a rapid biosensor for TDM of trastuzumab and ipilimumab with the potential to improve therapy. The sensitivity of this platform alongside its rapid action would be suitable for bedside monitoring in a point-of-care (PoC) setting.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Affimer protein; Herceptin; Humira; Rituxan; Therapeutic drug monitoring; Yervoy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Electronic & Electrical Engineering (Leeds) > Pollard Institute (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/N029976/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Jul 2023 10:17 |
Last Modified: | 11 Sep 2024 16:21 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bios.2023.115488 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201593 |