Insights from native mass spectrometry approaches for top- and middle- level characterization of site-specific antibody-drug conjugates.

ABSTRACT: Antibody-drug conjugates (ADCs) have emerged as a family of compounds with promise as efficient immunotherapies. First-generation ADCs were generated mostly via reactions on either lysine side-chain amines or cysteine thiol groups after reduction of the interchain disulfide bonds, resulting in heterogeneous populations with a variable number of drug loads per antibody. To control the position and the number of drug loads, new conjugation strategies aiming at the generation of more homogeneous site-specific conjugates have been developed. We report here the first multi-level characterization of a site-specific ADC by state-of-the-art mass spectrometry (MS) methods, including native MS and its hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS methodologies for

SUBMITTER: Botzanowski T 

PROVIDER: S-EPMC5524152 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature