Biological Evaluation of Cleavable Linkers in Exatecan-Based Antibody-Drug Conjugates: A Comparative Study of DXd and Exo-Linker Platforms.

ABSTRACT: Antibody-drug conjugates (ADCs) represent a transformative class of cancer therapies that combine the specificity of monoclonal antibodies with the cytotoxicity of potent drug payloads. This study presents the development and evaluation of a novel linker platform designed to enhance ADC stability and pharmacokinetics by addressing the limitations associated with traditional cleavable linkers. Using trastuzumab conjugated with a payload linker consisting of this platform and exo-EVC-Exatecan (APL-1082), we examined key parameters, including in vivo efficacy and pharmacokinetic profiles in rat models, to directly compare it with the clinically validated trastuzumab-deruxtecan (T-DXd, Enhertu). The resulting ADC demonstrated superior stability and maintained drug-to-antibody ratios (DA

SUBMITTER: Watanabe T 

PROVIDER: S-EPMC12409547 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature