Immunotherapy in acute myelogenous leukemia and myelodysplastic syndrome

Disease recurrence following successful bone marrow transplantation remains a major impediment in the management of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A variety of monoclonal antibodies that deliver drugs or toxins to the site of activity, have been used in an attempt to augment marrow transplantation. Examples of three different monoclonal antibody techniques (naked antibody, drug antibody conjugations, and radiolabeled antibodies) are discussed. CD33 is an attractive antigen to use as a target for treating AML because it is present on most AML cells. Naked antibodies are limited in their ability to kill tumor cells, although studies to date suggest there may be a role in antileukemic therapy for unlabeled anti-CD33 humanized M195 antibody after the tumor burden has been reduced by chemotherapy. Calicheamicin, a novel and toxic drug moiety conjugated to anti-CD33 antibody, is currently under investigation in patients with refractory or relapsed AML. Results from a Phase I investigation were encouraging. Three different radiolabeled monoclonal antibodies have been evaluated in Phase I/II studies--131I-labeled anti-CD33 (p67) antibody, 213Bi-labeled humanized M195 antibody, and 131I-anti-CD45 antibody. CD45 is a cell-surface antigen broadly expressed by all circulating leukocytes and lymphocytes. Initial studies demonstrated that substantially greater doses of radiation could be delivered to targeted organs compared with nontargeted organs using 131I-anti-CD45 antibody. This approach offers the potential for augmenting leukemia therapy without increased risk of toxicity.