Re-examined the Bystander Effect to Understand How Payload Properties & Tumor Microenvironment Influence Off-Target Toxicity
- Engineering an ADC panel with varying payload hydrophobicity to quantify how lipophilic payloads passively diffuse across cell membranes, establishing a predictive relationship between logD and off-target toxicities
- Investigating the contribution of membrane transporters to the bystander effect, including how influx and efflux mechanisms regulate intracellular payload accumulation and intercellular transfer, to determine their impact on off-target toxicity and therapeutic selectivity
- Correlating in vitro bystander killing potential in 3D spheroid co-cultures with in vivo outcomes to establish a predictive screening assay, enabling optimization of payload properties for an improved therapeutic index