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

• Published in: Nature communications Vol. 6; no. 1; p. 6645
• Main Authors: Maruani, Antoine, Smith, Mark E B, Miranda, Enrique, Chester, Kerry A, Chudasama, Vijay, Caddick, Stephen
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 31.03.2015; Nature Pub. Group
• Subjects: Antibodies - chemistry; Antibodies - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cell Line, Tumor; Chromatography, Liquid; Click Chemistry; Drug Delivery Systems - methods; Electrophoresis, Polyacrylamide Gel; Humans; Immunoconjugates - chemistry; Immunoconjugates - therapeutic use; Mass Spectrometry; Microscopy, Confocal; Photoelectron Spectroscopy; Receptor, ErbB-2 - metabolism; Trastuzumab - administration & dosage; Trastuzumab - chemistry
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7645

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.