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Issue 14, 2019
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Monodisperse polysarcosine-based highly-loaded antibody-drug conjugates

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Abstract

Antibody-drug conjugates (ADCs) convey highly potent anticancer drugs to antigen-expressing tumor cells, thereby sparing healthy tissues throughout the body. Pharmacokinetics and tolerability of ADCs are predominantly influenced by the drug-antibody ratio (DAR) of the conjugates, which is to-date limited to a value of 3–4 drugs per antibody in ADCs under clinical investigations. Here, we report the synthesis of monodisperse (i.e. discrete) polysarcosine compounds and their use as a hydrophobicity masking entity for the construction of highly-loaded homogeneous β-glucuronidase-responsive antibody-drug conjugates (ADCs). The highly hydrophilic drug-linker platform described herein improves drug-loading, physicochemical properties, pharmacokinetics and in vivo antitumor efficacy of the resulting conjugates.

Graphical abstract: Monodisperse polysarcosine-based highly-loaded antibody-drug conjugates

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Supplementary files

Article information


Submitted
17 Jan 2019
Accepted
05 Mar 2019
First published
06 Mar 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 4048-4053
Article type
Edge Article

Monodisperse polysarcosine-based highly-loaded antibody-drug conjugates

W. Viricel, G. Fournet, S. Beaumel, E. Perrial, S. Papot, C. Dumontet and B. Joseph, Chem. Sci., 2019, 10, 4048
DOI: 10.1039/C9SC00285E

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    [Original citation] - Published by The Royal Society of Chemistry.

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