title: The past and future of CD33 as therapeutic target in acute myeloid leukemia.
abstract: CD33 is a myeloid differentiation antigen with endocytic properties. It is broadly expressed on acute myeloid leukemia (AML) blasts and, possibly, some leukemic stem cells and has therefore been exploited as target for therapeutic antibodies for many years. The improved survival seen in many patients when the antibody-drug conjugate, gemtuzumab ozogamicin, is added to conventional chemotherapy validates this approach. However, many attempts with unconjugated or conjugated antibodies have been unsuccessful, highlighting the challenges of targeting CD33 in AML. With the development of improved immunoconjugates and CD33-directed strategies that harness immune effector cells, therapeutics with enhanced efficacy may soon become available. Toxic effects on normal hematopoietic cells may increase in parallel with this increased efficacy and demand new supportive care measures, including possibly rescue with donor cells, to minimize morbidity and mortality from drug-induced cytopenias and to optimize treatment outcomes with these agents in patients with AML.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: George S
authors.initials: GS
authors.lastname: Laszlo
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA.
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA. Electronic address: rwalter@fhcrc.org.
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D063268:Sialic Acid Binding Ig-like Lectin 3
keywords: Acute myeloid leukemia; Antibody; Antibody-drug conjugate; BiTE; Bispecific antibody; CD33; Chimeric antigen receptor; Gemtuzumab ozogamicin; Immunotherapy; Radioimmunoconjugate