New agents for the treatment of acute myeloid leukemia: gemtuzumab ozogamicin

The CD33 antigen is a 67-kD sialic acid-dependent adhesion protein that is specific for myeloid cells. CD33 is expressed on approximately 90% of AML cases, as defined by the presence of the antigen on greater than 20% of the leukemic blasts, but not on normal CD34+ pluripotent hematopoietic stem cells or nonhematopoietic tissues.1 Gemtuzumab ozogamicin consists of a semisynthetic derivative of calicheamicin, a potent cytotoxic antibiotic, linked to a humanized IgG4 anti-CD33 monoclonal antibody (hP67.6). The hP67.6 antibody is non-cytotoxic by itself.2 In vitro data indicate that when GO binds the CD33 antigen, the complex is rapidly internalized.3,4 Upon internalization, the calicheamicin derivative is released inside the lysosomes of the myeloid cell by acid hydrolysis. The released calicheamicin derivative binds to DNA in the minor groove resulting in DNA double strand breaks and cell death by apoptosis.