HER2 | Cancer drug screening | PDXO

Antibody-drug conjugates (ADCs) are a promising class of targeted cancer therapies, but assessing their efficacy across HER2-driven cancers requires physiologically relevant, clinically annotated models. Traditional 2D cultures fail to recapitulate HER2 expression patterns and tumor architecture, limiting translational utility.

Champions Oncology developed a high-throughput screening (HTS) platform using HER2-positive patient-derived 3D organoids (PDXOs) from its Champions TumorGraft3D (CTG3D) platform. These models reflect clinical HER2 expression (confirmed via IHC and flow cytometry) and are derived from well-characterized PDX lines, enabling robust, scalable evaluation of HER2-targeted therapies.

CTG3D HER2+ organoids were screened with FDA-approved ADCs (e.g., T-DM1, T-Dxd) and free payloads (DM1, Exatecan). The organoids maintained 3D architecture and HER2 expression, and drug responses were consistent with known pharmacological profiles.
IC50 values showed superior potency for ADCs versus isotype or naked antibodies, aligning with HER2 status. Normalized delta AUC values (30–50% for HER2+ vs. ~20% for HER2–) confirmed differential ADC activity. Assay reproducibility and HER2-dependent drug sensitivity underscored model fidelity.
This ex vivo 3D model platform supports precise evaluation of HER2-targeted ADCs, providing a powerful tool for preclinical drug discovery, payload comparison, and prioritization of ADC candidates for clinical development.

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HER2-positive patient-derived xenograft organoids (PDXOs) as a novel preclinical tool to evaluate new therapies against HER2-driven cancers