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Review
. 2017 Nov 9;5(4):64.
doi: 10.3390/biomedicines5040064.

Site-Specific Antibody Conjugation for ADC and Beyond

Qun Zhou  1
Affiliations
Review

Site-Specific Antibody Conjugation for ADC and Beyond

Qun Zhou. Biomedicines. .

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.

Keywords: ADC; glycans; other applications; short peptide tags; site-specific conjugation; specific amino acids; unnatural amino acids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Binding and internalization of antibody-drug conjugate (ADC) followed by the release of its cytotoxins inside the cell.
Figure 2
Figure 2
The categories of the site-specific ADC with cytotoxin coupled at unique and defined sites in an antibody molecule.
Figure 3
Figure 3
The application of the site-specific ADCs in coupling antibody with small protein, radioisotope, and non-cytotoxic compounds.
See this image and copyright information in PMC

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References

    1. Reichert J.M. Antibodies to watch in 2017. Money Adv. Budg. Serv. 2017;9:167–181. doi: 10.1080/19420862.2016.1269580. - DOI - PMC - PubMed
    1. Ecker D.M., Jones S.D., Levine H.L. The therapeutic monoclonal antibody market. Money Adv. Budg. Serv. 2015;7:9–14. doi: 10.4161/19420862.2015.989042. - DOI - PMC - PubMed
    1. Alley S.C., Okeley N.M., Senter P.D. Antibody-drug conjugates: Targeted drug delivery for cancer. Curr. Opin. Chem. Biol. 2010;14:529–537. doi: 10.1016/j.cbpa.2010.06.170. - DOI - PubMed
    1. Beck A. Review of Antibody-Drug Conjugates, Methods in Molecular Biology series: A book edited by Laurent Ducry. Money Adv. Budg. Serv. 2014;6:30–33. doi: 10.4161/mabs.27005. - DOI
    1. Carter P.J., Senter P.D. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14:154–169. doi: 10.1097/PPO.0b013e318172d704. - DOI - PubMed