title: A plug-and-play approach to antibody-based therapeutics via a chemoselective dual click strategy.
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.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
authors.forename: Antoine
authors.initials: A
authors.lastname: Maruani
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
authors.forename: Mark E B
authors.initials: ME
authors.lastname: Smith
authors.affiliation: UCL Cancer Institute, 72 Huntley Street, London WC1E 6BT, UK.
authors.forename: Enrique
authors.initials: E
authors.lastname: Miranda
authors.affiliation: UCL Cancer Institute, 72 Huntley Street, London WC1E 6BT, UK.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Chester
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
authors.forename: Vijay
authors.initials: V
authors.lastname: Chudasama
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Caddick
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D057930:Click Chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000627:therapeutic use; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D056951:Photoelectron Spectroscopy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
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