Successful ADCs must achieve potent on-target cytotoxicity while minimizing off-target effects on healthy cells. Off-target toxicities to normal hematopoietic cells are the most frequently reported adverse events associated with ADCs. These off-target effects can be caused when normal cells express the ADC target. However, the unforeseen and unexpected off-target toxicities to the hematopoietic compartment, with targets not expressed on hematopoietic cells, suggest that linker stability and the highly potent payloads may play the most significant role in off-target toxicity.
Watch this video to learn how in vitro assays can be used to quickly evaluate these components and demonstrate how linker stability and payload selection contribute to these adverse outcomes, resulting in more successful ADC programs.