Campbell, E., Adamson, H., Luxton, T. et al. (4 more authors) (2024) Therapeutic drug monitoring of immunotherapies with novel Affimer–NanoBiT sensor construct. Sensors & Diagnostics.
Abstract
Concentration–therapeutic efficacy relationships have been observed for several therapeutic monoclonal antibodies (TmAb), where low circulating levels can result in ineffective treatment and high concentrations can cause adverse reactions. Rapid therapeutic drug monitoring (TDM) of TmAb drugs would provide the opportunity to adjust an individual patient's dosing regimen to improve treatment results. However, TDM for immunotherapies is currently limited to centralised testing methods with long sample-collection to result timeframes. Here, we show four point-of-care (PoC) TmAb biosensors by combining anti-idiotypic Affimer proteins and NanoBiT split luciferase technology at a molecular level to provide a platform for rapid quantification (<10 minutes) for four clinically relevant TmAb (rituximab, adalimumab, ipilimumab and trastuzumab). The rituximab sensor performed best with 4 pM limit of detection (LoD) and a quantifiable range between 8 pM–2 nM with neglectable matrix effects in serum up to 1%. After dilution of serum samples, the resulting quantifiable range for all four sensors falls within the clinically relevant range and compares favourably with the sensitivity and/or time-to-result of current ELISA standards. Further development of these sensors into a PoC test may improve treatment outcome and quality of life for patients receiving immunotherapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Author(s). Published by the Royal Society of Chemistry Open Access Article. Published on 01 November 2023. Downloaded on 1/5/2024 9:42:46 AM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Synthetic Biology (Leed) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/N029976/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Jan 2024 11:26 |
Last Modified: | 21 Jun 2024 14:00 |
Published Version: | http://dx.doi.org/10.1039/d3sd00126a |
Status: | Published |
Publisher: | Royal Society of Chemistry (RSC) |
Identification Number: | 10.1039/d3sd00126a |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:207208 |