Using a High-Throughput Microphysiological System to Model ADC- and Chemotherapy-Induced Peripheral Neuropathy

Explore how advanced microphysiological systems can bridge the gap between preclinical safety models and clinical outcomes in this 21-minute webinar presented by Dr. Kristin Bircsak from AstraZeneca. Learn about the development and application of a high-throughput in vitro model using human iPSC-derived peripheral neurons embedded in the OrganoPlate® 3D microfluidic culture platform to predict peripheral neuropathy, a dose-limiting side effect of chemotherapeutic and antibody drug conjugate treatments. Discover how this innovative axonal outgrowth model successfully captures dose- and time-dependent neurotoxicity across clinically relevant concentration ranges, enabling researchers to rank compounds by their neurotoxic potential. Examine the methodology behind testing 40 chips simultaneously over multiple timepoints using calcein-AM labeling and confocal microscopy to quantify axonal network disruption. Understand how these advanced cell models can enhance early selection of safer oncology therapeutics by providing predictive assessment capabilities that standard preclinical toxicology studies often miss, particularly for MMAE-ADCs where peripheral neuropathy has high clinical incidence but poor preclinical prediction. Gain insights into interpreting axonal outgrowth data for improved molecular selection and learn how microphysiological systems may reduce dependence on animal toxicology models while improving clinical success rates for cancer therapeutics.