One of the challenges with ADC treatment is off-target toxicity to hematopoietic cells resulting in neutropenia, severe anemia and thrombocytopenia. It is caused by unintended release of the payload from the construct. Therefore, many ADCs, where the
antibody targets specific diseased proteins (e.g., HER-2) and which are not present on hematopoietic cells, may still have hematopoietic toxicity (off-target toxicity). The generation of ADCs that target proteins on diseased cells, for example
Belantamab mafodotin, an ADC targeting B-cell maturation antigen (BCMA) on multiple myeloma (MM) cells, aims at killing the diseased cells (on-target efficacy) while sparing the normal hematopoietic cells.
