Developing Tumor Models to Decode Engineered SIRPα PDC Target Dependency & Overcome MMAE Resistance Across Cancer Indications
- Using CD47 KO isogenic lines across multiple cancer types to confirm that payload delivery requires eSIRPα-CD47 engagement, defining the therapeutic window and assessing activity across diverse tumor indications
- Outlining the model-selection strategy for stress-testing eSIRPα-based PDCs, covering how CD47-targeted tumor systems are engineered to elicit drug resistance
- Demonstrating that eSIRPα-siRNA conjugates silencing efflux pump genes restore MMAE sensitivity in resistant tumors, establishing proof-of-concept for combining targeted gene silencing with cytotoxic payload delivery