Mechanistic insights into the rational design of masked antibodies.

ABSTRACT: Although monoclonal antibodies have greatly improved cancer therapy, they can trigger side effects due to on-target, off-tumor toxicity. Over the past decade, strategies have emerged to successfully mask the antigen-binding site of antibodies, such that they are only activated at the relevant site, for example, after proteolytic cleavage. However, the methods for designing an ideal affinity-based mask and what parameters are important are not yet well understood. Here, we undertook mechanistic studies using three masks with different properties and identified four critical factors: binding site and affinity, as well as association and dissociation rate constants, which also played an important role. HDX-MS was used to identify the location of binding sites on the antibody, which were subse

SUBMITTER: Orozco CT 

PROVIDER: S-EPMC9272835 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature