ADC efficacy and safety evaluation poster featuring PDX organoids data, heatmaps, assay results, and PDF download option on Pharmaron-branded layout.

ADC Efficacy and Safety Evaluation Based on Organoid Models

We present a case study showcasing the testing of antibody-drug conjugates (ADC) for efficacy and safety on organoids derived from patient-derived xenograft (PDX) models and organoids derived from healthy intestinal tissue.

This study highlights the platform’s capabilities demonstrated through ADCs that target HER2.

  • Over 150 PDX organoid (PDXO) models from diverse cancer types and normal organoids from intestinal tissue were developed.
  • HER2 expression was assessed via multi-omics platforms RNAseq, WES, Western blot, and IHC staining.
  • Organoid viability testing was performed on 14 PDXO models with varying HER2 levels using four ADCs and their payload and payload+linker controls.
  • Safety evaluation was conducted using intestinal organoids.

Key findings:

  • Efficacy: High HER2 expression correlated with increased sensitivity to ADC treatment, while lower expression indicated resistance. Payloads alone caused broad cytotoxicity.
  • Safety: Intestinal organoids showed minimal response to ADCs, revealing a favorable therapeutic window with reduced gastrointestinal side effects.