Understanding the Source of Toxicity to Create a Strategic Framework for Distinguishing Payload vs. Target-Mediated Effects
- Employing a matched-pair strategy using inert payloads and non-binding antibodies, to systematically isolate and quantify the contributions of payload and target engagement to overall observed toxicity, providing a clear mechanistic attribution for dose-limiting adverse events
- Utilizing tissue microarrays with quantitative immunohistochemistry for target expression, to map the biodistribution of target antigens in critical normal organs,creating a preclinical risk assessment tool for on-target toxicity before candidate selection
- Developing computational toxicology models that partition free payload and intact ADC concentrations, to predict which component is driving clinical adverse events, informing linker design strategies to minimize systemic payload release