Gemtuzumab

Use

Gemtuzumab ozogamicin (Mylotarg, fusion molecule) isan MAb derived from the CD33 antigen, a sialic aciddependentadhesion protein expressed on the surface ofleukemia blasts and immature normal cells of myelomonocyticorigin but not on normal hematopoietic stem cells. Gemtuzumab ozogamicin is indicated for the treatmentof patients with CD33-positive acute myeloid leukemia infirst relapse among adults 60 years of age or older who arenot considered candidates for cytotoxic chemotherapy.Gemtuzumab ozogamicin binds to the CD33 antigen expressedby hematopoietic cells. This antigen is expressed onthe surface of leukemic blasts in more than 80% of patientswith acute myeloid leukemia. CD33 is also expressed onnormal and leukemic myeloid colony-forming cells, includingleukemic clonogenic precursors, but it is not expressedon pluripotent hematopoietic stem cells or nonhematopoieticcells. Binding of the anti-CD33 antibody results in acomplex that is internalized. On internalization thecalicheamicin derivative is released inside the lysosomes ofthe myeloid cells. The released calicheamicin derivativebinds to the minor groove of DNA and causes double-strandbreaks and cell death.