All-in-one disulfide bridging enables the generation of antibody conjugates with modular cargo loading.

ABSTRACT: Antibody-drug conjugates (ADCs) are valuable therapeutic entities which leverage the specificity of antibodies to selectively deliver cytotoxins to antigen-expressing targets such as cancer cells. However, current methods for their construction still suffer from a number of shortcomings. For instance, using a single modification technology to modulate the drug-to-antibody ratio (DAR) in integer increments while maintaining homogeneity and stability remains exceptionally challenging. Herein, we report a novel method for the generation of antibody conjugates with modular cargo loading from native antibodies. Our approach relies on a new class of disulfide rebridging linkers, which can react with eight cysteine residues, thereby effecting all-in-one bridging of all four interchain disulfides

SUBMITTER: Dannheim FM 

PROVIDER: S-EPMC9350601 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature