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Champions Oncology AACR Poster 4006_Chou_Final_16Apr2025.pdf

Poster

AACR 2025 Poster

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

Summary

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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