The clinical efficacy of an ADC is heavily influenced by its ability to selectively target its designated epitope, however ADCs exhibit high off-target toxicity to tissues without epitope expression, thus limiting clinical efficacy. Trastuzumab vedotin, which targets human epidermal growth factor receptor 2 (HER2) which is not present on hematopoietic cells, still demonstrates off-target toxicity to hematopoietic progenitors. On-target efficacy was evaluated with Gemtuzumab ozogamicin, targeting CD33-positive AMLs, and Belantamab mafodotin, targeting B-cell maturation antigen (BCMA) in MM. We evaluated an in-vitro platform to characterize potential efficacy and hematological toxicity (neutropenia) associated with ADCs in patients with AML, MM, and normal bone marrow.
