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Study of the Interaction of Trastuzumab and SKOV3 Epithelial Cancer Cells Using a Quartz Crystal Microbalance Sensor
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
2015 (English)In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 15, no 3, 5884-5894 p.Article in journal (Refereed) Published
Abstract [en]

Analytical methods founded upon whole cell-based assays are of importance in early stage drug development and in fundamental studies of biomolecular recognition. Here we have studied the binding of the monoclonal antibody trastuzumab to human epidermal growth factor receptor 2 (HER2) on human ovary adenocarcinoma epithelial cancer cells (SKOV3) using quartz crystal microbalance (QCM) technology. An optimized procedure for immobilizing the cells on the chip surface was established with respect to fixation procedure and seeding density. Trastuzumab binding to the cell decorated sensor surface was studied, revealing a mean dissociation constant, K-D, value of 7 +/- 1 nM (standard error of the mean). This study provides a new perspective on the affinity of the antibody-receptor complex presented a more natural context compared to purified receptors. These results demonstrate the potential for using whole cell-based QCM assay in drug development, the screening of HER2 selective antibody-based drug candidates, and for the study of biomolecular recognition. This real time, label free approach for studying interactions with target receptors present in their natural environment afforded sensitive and detailed kinetic information about the binding of the analyte to the target.

Place, publisher, year, edition, pages
2015. Vol. 15, no 3, 5884-5894 p.
Keyword [en]
quartz crystal microbalance, breast cancer, cell-based biosensor, Herceptin, trastuzumab, HER2
National Category
Chemical Sciences Medical Engineering
URN: urn:nbn:se:uu:diva-256551DOI: 10.3390/s150305884ISI: 000354160900066PubMedID: 25763651OAI: oai:DiVA.org:uu-256551DiVA: diva2:826020
Available from: 2015-06-24 Created: 2015-06-24 Last updated: 2016-02-23Bibliographically approved

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Nicholls, Ian A.
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