SHR-A1811, a novel anti-HER2 antibody-drug conjugate with optimal drug-to-antibody ratio, efficient tumor killing potency, and favorable safety profiles.

ABSTRACT: HER2-targeting antibody-drug conjugates (ADCs), especially trastuzumab deruxtecan (T-DXd), have revolutionized the treatment landscape of HER2-expressing or mutant cancers. However, undesired adverse events are still inevitable and it is necessary to discover a HER2-directed ADC with better safety profiles. SHR-A1811 is composed of trastuzumab, a cleavable linker and a novel topoisomerase I inhibitor, SHR169265. The results indicated that SHR169265 shows better permeability, strong cytotoxicity and faster systemic clearance than DXd analog (SHR197971). The drug-to-antibody ratio (DAR) of SHR-A1811 was optimized as 6 via balancing efficacy and toxicity. SHR-A1811 showed HER2-dependent growth inhibition against various cell lines and desirable bystander killing capability. SHR-A1811 led to t

SUBMITTER: Zhang T 

PROVIDER: S-EPMC12200682 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature