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Biomedicines 2017, 5(4), 64; doi:10.3390/biomedicines5040064

Site-Specific Antibody Conjugation for ADC and Beyond

Protein Engineering, Biologics Research, Sanofi, Framingham, MA 01701, USA
Received: 18 October 2017 / Revised: 4 November 2017 / Accepted: 7 November 2017 / Published: 9 November 2017
(This article belongs to the Special Issue Immunoconjugates)
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Abstract

Antibody-drug conjugates (ADCs) have become a promising class of antitumor agents with four conjugates being approved by regulatory agencies for treating cancer patients. To improve the conventional conjugations that are currently applied to generate these heterogeneous products, various site-specific approaches have been developed. These methods couple cytotoxins or chemotherapeutic drugs to specifically defined sites in antibody molecules including cysteine, glutamine, unnatural amino acids, short peptide tags, and glycans. The ADCs produced showed high homogeneity, increased therapeutic index, and strong antitumor activities in vitro and in vivo. Moreover, there are recent trends in using these next generation technologies beyond the cytotoxin-conjugated ADC. These site-specific conjugations have been applied for the generation of many different immunoconjugates including bispecific Fab or small molecule–antibody conjugates, immunosuppressive antibodies, and antibody–antibiotic conjugates. Thus, it is likely that additional technologies and related site-specific conjugates will emerge in the near future, with various chemicals or small molecular weight proteins in addition to cytotoxin for better treatment of many challenging diseases. View Full-Text
Keywords: site-specific conjugation; specific amino acids; unnatural amino acids; glycans; short peptide tags; ADC; other applications site-specific conjugation; specific amino acids; unnatural amino acids; glycans; short peptide tags; ADC; other applications
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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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Zhou, Q. Site-Specific Antibody Conjugation for ADC and Beyond. Biomedicines 2017, 5, 64.

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