Monodisperse polysarcosine-based highly-loaded antibody-drug conjugates.
Chem Sci
; 10(14): 4048-4053, 2019 Apr 14.
Article
in En
| MEDLINE
| ID: mdl-31015945
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 ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Chem Sci
Year:
2019
Document type:
Article