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Poster

SITC 2025 Poster #1245

Evaluating the Efficacy of Targeted Therapies in HER2-Driven Cancers Using Patient-Derived Xenograft Organoids

Summary

Antibody drug conjugates rise or fall on the details, target density, internalization, payload potency, and linker behavior. This study uses HER2-positive PDX-derived organoids that preserve patient biology to profile ADC constructs, free payloads, and controls in a high-throughput, 96-well format. We confirm HER2 status by IHC and flow, establish a reproducible assay with strong Z prime performance, and generate IC50s that differentiate targeted activity from background effects. The goal is practical, faster construct selection, cleaner go or no go decisions, and better alignment with downstream in vivo work.

We screened and confirmed HER2 expression in CTG3D PDXO models, established a reproducible viability assay, and profiled ADCs, free payloads, and isotype controls to derive IC50 values. The study highlights differential cytotoxicity driven by construct elements, including linker effects, and shows consistency with clinical annotations of HER2 status. Findings support model selection, construct optimization, and earlier go or no go decisions in HER2 programs.

Learning outcomes:

  • Understand how HER2 expression is verified in CTG3D PDXOs using IHC and flow, and how those results align with clinical annotation.

  • See how a high-throughput 96-well workflow with strong Z prime enables reliable IC50 calculations for ADCs, payloads, and isotype controls.

  • Recognize how target status and linker chemistry shape response profiles in a native-like tumor microenvironment.

  • Learn a practical approach to select models and compare constructs before moving to in vivo, improving the odds of translational success.

  • Identify next steps to extend these findings, for example correlation with in vivo data or expansion into combination designs.

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