Delivery strategies for immune checkpoint blockade

Properties of Leukemic Stem Cells in Regulating Drug Resistance in Acute and Chronic Myeloid Leukemias

“…Furthermore, as another therapeutic modality, ADCs are typically composed of a cytotoxic payload chemically connected to a monoclonal antibody via a biodegradable linker, whereby the antibody component mediates the specific delivery of the payload into target cells to minimize unintentional cytotoxicity. A classic example is gemtuzumab ozogamicin (GO) [ 221 , 222 ], which consists of calicheamicin linked to an anti-CD33 antibody and has entered multiple phase III clinical trials for adult and pediatric AML patients harboring diverse cytogenetic phenotypes, such as nucleophosmin1 ( NPM1 )-mutated [ 223 ] and lysine methyltransferase 2A ( KMT2A )-rearranged AML subtypes [ 224 , 225 ]. Importantly, it has been shown that GO is effective in managing minimal residual disease and drastically reduces chemo-residual leukemic-initiating cells upon incorporation into conventional induction chemotherapy [ 226 , 227 ].…”