A plug-and-play approach to antibody-based therapeutics via a chemoselective dual click strategy

Antoine Maruani, Mark E.B. Smith, Enrique Miranda, Kerry A. Chester, Vijay Chudasama () and Stephen Caddick ()
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Antoine Maruani: University College London
Mark E.B. Smith: University College London
Enrique Miranda: UCL Cancer Institute
Kerry A. Chester: UCL Cancer Institute
Vijay Chudasama: University College London
Stephen Caddick: University College London

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract Although recent methods for the engineering of antibody–drug conjugates (ADCs) have gone some way to addressing the challenging issues of ADC construction, significant hurdles still remain. There is clear demand for the construction of novel ADC platforms that offer greater stability, homogeneity and flexibility. Here we describe a significant step towards a platform for next-generation antibody-based therapeutics by providing constructs that combine site-specific modification, exceptional versatility and high stability, with retention of antibody binding and structure post-modification. The relevance of the work in a biological context is also demonstrated in a cytotoxicity assay and a cell internalization study with HER2-positive and -negative breast cancer cell lines.

Date: 2015
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DOI: 10.1038/ncomms7645

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