Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate

There are several competing models of stem cell involvement in acute myeloid leukemia (AML). At issue is whether the disease origin is in the pluripotent stem cell or whether it arises later in a more mature progenitor cell. The observation that the CD33 antigen is present on AML cells, and on normal and leukemic progenitors, suggested that one might be able to target these cells while sparing the normal stem cells. Response rates of acute myelogenous leukemia patients treated with the newly developed anti-CD33 antibody-calicheamicin conjugate suggest that at least for a proportion of patients early precursors responsible for re-establishing hematopoiesis are likely to be predominantly normal in origin.