Switching positions: Assessing the dynamics of conjugational heterogeneity in antibody-drug conjugates using CE-SDS.

ABSTRACT: Antibody-drug conjugates (ADCs) are a prospective class of new oncology therapeutics with the ability to deliver a cytotoxic drug to a targeted location. The concept appears simple, but ADCs are highly complex due to their intrinsic heterogeneity. Randomly conjugated ADCs, for instance, are composed of conjugated species carrying between 0 and 8 linker-drug molecules, with several positional isomers that vary in drug distribution across the antibody. The drug load, expressed as drug-to-antibody ratio (DAR), is a critical quality attribute and should be well controlled, together with the distribution of drug molecules. Here, the impact of the duration of disulfide bond reduction on the DAR was investigated by quantitating the (isomeric) DAR species in ADCs produced with varying reduction ti

SUBMITTER: van den Berg EBA 

PROVIDER: S-EPMC10086850 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature