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Open AccessArticle

A RAGE-Targeted Antibody-Drug Conjugate: Surface Plasmon Resonance as a Platform for Accelerating Effective ADC Design and Development

1
Institute of Life Science, Swansea University Medical School, Swansea University, Swansea, SA2 8PP, UK
2
GE Healthcare Bio-Sciences, SE-751 84 Uppsala, Sweden
3
GE Healthcare, Little Chalfont, Buckinghamshire, HP7 9NA, UK
*
Author to whom correspondence should be addressed.
Antibodies 2019, 8(1), 7; https://doi.org/10.3390/antib8010007
Received: 25 November 2018 / Revised: 14 December 2018 / Accepted: 21 December 2018 / Published: 7 January 2019
(This article belongs to the Special Issue Antibody-Drug Conjugate)
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Abstract

Antibodies, antibody-like molecules, and therapeutics incorporating antibodies as a targeting moiety, such as antibody-drug conjugates, offer significant potential for the development of highly efficacious drugs against a wide range of disorders. Despite some success, truly harnessing the superior targeting properties of these molecules requires a platform from which to effectively identify the best candidates for drug development. To streamline the development of antibody-drug conjugates targeting gynecological cancers within our laboratory, we incorporated surface plasmon resonance analysis (Biacore™ T200) into our development toolkit. Antibodies, selected based on positive ELISA screens as suitable for development as antibody-drug conjugates, were evaluated using surface plasmon resonance to determine a wide range of characteristics including specificity, kinetics/affinity, the effect of linker binding, the impact of the drug to antibody ratio, and the effect of endosomal pH on antibody-antigen binding. Analysis revealed important kinetics data and information regarding the effect of conjugation and endosomal pH on our antibody candidates that correlated with cell toxicity and antibody internalization data. As well as explaining observations from cell-based assays regarding antibody-drug conjugate efficacies, these data also provide important information regarding intelligent antibody selection and antibody-drug conjugate design. This study demonstrates the application of surface plasmon resonance technology as a platform, where detailed information can be obtained, supporting the requirements for rapid and high-throughput screening that will enable enhanced antibody-drug conjugate development. View Full-Text
Keywords: surface plasmon resonance; antibody-drug conjugates; antibodies; gynecological cancers; binding kinetics surface plasmon resonance; antibody-drug conjugates; antibodies; gynecological cancers; binding kinetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Healey, G.D.; Frostell, A.; Fagge, T.; Gonzalez, D.; Conlan, R.S. A RAGE-Targeted Antibody-Drug Conjugate: Surface Plasmon Resonance as a Platform for Accelerating Effective ADC Design and Development. Antibodies 2019, 8, 7.

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