AACR-NCI-EORTC 2025 Poster B058

Antitumor Activity of HER2 Antibody-drug Conjugates (ADCs) Against Tumors with Different HER2 Expression Levels

Aaron Li Hua, Jian Feng, Chenpan Nie, Jun Zhou, Ludovic Bourre, Jessie JingJing Wang

In this study, Crown Bioscience established a panel of breast, gastric, NSCLC, pancreatic, colorectal, and glioma models with variable HER2 expression to evaluate the anti-tumor activity of Trastuzumab deruxtecan (T-DXD) and Trastuzumab emtansine (T-DM1). This robust preclinical platform provides a translational bridge for developing and optimizing next-generation HER2-targeted ADCs.

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• HER2 Expression–Driven Response: Characterize differential efficacy of T-DXD and T-DM1 across models with high, medium, and low HER2 expression using in vitro IC₅₀ and in vivo TGI analysis.
  
  
• Superior Efficacy of T-DXD: Explore how T-DXD achieves near-complete tumor regression in HER2-high models and partial response in HER2-low models, outperforming T-DM1 across tumor types.
  
  
• Bystander Killing Demonstration: See how T-DXD induces regression in mixed HER2⁺/HER2⁻ xenografts—highlighting its potent bystander effect not observed with T-DM1.
  
  
• Validated Translational Models: Leverage paired cell line and CDX models to study ADC mechanisms of action (MOA) and accelerate HER2-targeted therapy development.

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