ADC Development Revolution: Leveraging Translational Models for Next-Generation Cancer Therapeutics

In the rapidly evolving landscape of oncology drug discovery, antibody-drug conjugates (ADCs) represent one of the most promising therapeutic modalities. In this CrownCast episode, Benjamin Wilkin, Product Marketing Manager at Crown Bioscience, sits down with David Ouyang, SVP of Innovation at Crown Bioscience, to explore how advanced translational models are transforming ADC development and overcoming the unique challenges of this complex therapeutic class.

ADCs: Biological Missiles Against Cancer

ADCs have evolved from niche biologics to mainstream therapeutics, with multiple approvals targeting various tumor-associated antigens. As Davy explains, "I really like the analogy of describing ADC as a biological missile against cancer. The antibody really serves as a targeting system where it seeks out and binds to the specific tumor-associated antigens on the tumor cells."

This sophisticated approach has led to record-breaking licensing deals, making ADCs a powerful growth engine for biotechnology companies.

Navigating Complexity Through Integrated Modeling

The intricate nature of ADCs demands sophisticated testing approaches. With over 60 targets tested clinically and multiple variables including antibody formats, linker chemistry, and payload classes, Davy emphasizes: "Every different target behaves very differently across tumor types. Their expression level, internalization mechanism, and tissue distribution differ."

Crown's integrated platform combines over 800 organoid models and 2,700 PDX models, enhanced by comprehensive biomarker analysis. "We can use the organoid platform for high throughput cytotoxicity screening, and then extend that insight into our PDX platform, where we capture the tumor heterogeneity, stromal contexts, and vasculature."

Strategic Model Selection and Operational Excellence

Successful ADC development requires strategic deployment of different model systems. Organoid models excel during discovery for rapid screening, while PDX models become essential for studying PKPD relationships and toxicity profiles. "It's not about choosing one model platform over another. They serve complementary roles in ADC R&D process."

Crown has addressed timeline challenges through operational optimization, delivering organoid screening results within six weeks and building collections of treatment-resistant models that mirror real-world patient populations.

The Path Forward: Precision Medicine and Partnership

The future lies in precision medicine approaches enabled by co-clinical programs that align preclinical data with ongoing trials. By integrating comprehensive biomarker assays and spatial omics, Crown maps target distribution to identify patient subgroups likely to benefit from specific ADC designs.

This integrated approach combining advanced model systems with deep data science capabilities is driving more predictive, efficient, and personalized ADC development programs that deliver meaningful benefits to cancer patients.