anti-CD33 antibody-drug conjugate BL-M11D1

An antibody-drug conjugate (ADC) composed of gemtuzumab, an immunoglobulin G4 (IgG4) monoclonal antibody directed against the CD33 antigen, conjugated, via a cathepsin B-cleavable linker, to the camptothecin derivative and topoisomerase 1 inhibitor Ed-04, with potential antineoplastic activity. Upon administration of anti-CD33 ADC BL-M11D1, gemtuzumab specifically targets and binds to the cell surface antigen CD33 expressed on myeloid leukemia cells. Upon binding, internalization and linker cleavage, Ed-04 is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and apoptosis in tumor cells that express CD33. Gemtuzumab may also induce an antibody-dependent cellular cytotoxicity (ADCC) against CD33-expressing tumor cells. CD33 is expressed on normal non-pluripotent hematopoietic stem cells and myeloid leukemia cells.