Antibody Drug Conjugates (ADCs) represent a relatively new class of cancer therapeutics. Their design involves a tumor-specific antibody, a linker and a potent payload.
In addition to the targeted killing of antigen-positive tumor cells, some ADCs appear to have significant off-target effects, causing neutropenia and thrombocytopenia, which have necessitated some clinical trials to be terminated early. However, the success of some ADCs at treating diseases has stimulated the continued research of ADCs as well as an increased ADC development. Publications by Zhao et al (2017) suggested that extracellular cleavage of the linker was responsible for cytotoxicity to differentiating neutrophils, whereas internalization of the ADCs by macropinocytosis induced thrombocytopenia.
We developed a platform to assess ADCs and address the specific bystander effects of the payload.