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Nat Commun. 2015 Mar 31;6:6645. doi: 10.1038/ncomms7645.

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

Author information

1
Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
2
UCL Cancer Institute, 72 Huntley Street, London WC1E 6BT, UK.

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.

PMID:
25824906
PMCID:
PMC4389247
DOI:
10.1038/ncomms7645
[Indexed for MEDLINE]
Free PMC Article

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