Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.

ABSTRACT: Antibody-drug conjugates (ADCs) are effective targeted therapeutics but are limited in their ability to incorporate less-potent payloads, varied drug mechanisms of action, different drug release mechanisms and tunable drug-to-antibody ratios. Here we introduce a technology to overcome these limitations called 'antibody-bottlebrush prodrug conjugates' (ABCs). An ABC consists of an IgG1 monoclonal antibody covalently conjugated to the terminus of a compact bivalent bottlebrush prodrug that has payloads bound through cleavable linkers and polyethylene glycol branches. This design enables the synthesis of ABCs with tunable average drug-to-antibody ratios up to two orders of magnitude greater than those of traditional ADCs. We demonstrate the functional flexibility and manufacturing efficiency

SUBMITTER: Liu B 

PROVIDER: S-EPMC12425459 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature