Abstract

Generation of a Novel Antibody Drug Conjugate using Platinum as a Linker

Monideepa Roy, Director, Invictus Oncology Pvt Ltd

Despite the advances in the design of antibody drug conjugates (ADCs), the search is still on for novel approaches that lead to increased stability and homogeneity. We report, for the first time, a novel ADC platform technology using a Pt (II)-based linker that conjugates to the cysteine residues and re-bridges the antibody chains covalently, imparting stability, site-specificity and homogeneity, which effectively overcomes the current limitations in the field. With anti-EGFR and anti-HER2 antibodies and camptothecin as payload, we have demonstrated that the resulting ADC was stable in human plasma and showed target-specific nanomolar potency in vitro. Treatment of human lung carcinoma xenografts with the ADC led to significant tumor growth inhibition by induction of apoptosis. The Pt-based ADCs can emerge as a simple and exciting proposition to address the limitations of current ADC linker technology.