Platform: Established a comprehensive ADC-resistant cell panel comprising 25 RI-characterized models with multi-omics profiling (WES/RNA- seq), enabling systematic evaluation of ADC efficacy and resistance mechanisms.
Mechanisms: Identified convergent and lineage-specific resistance drivers including efflux activation, target loss, and DNA repair upregulation, informing next-generation ADC design.
Application: Established a scalable framework for ADC optimization by leveraging the cell panel to construct customized resistant models, enabling prospective assessment of ADC potency and resistance liability, identification of resistance-overcoming candidates, and rational design of dual-payload ADCs with improved durability.
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