title: What happened to anti-CD33 therapy for acute myeloid leukemia?
abstract: CD33, a 67-kDa glycoprotein expressed on the majority of myeloid leukemia cells as well as on normal myeloid and monocytic precursors, has been an attractive target for monoclonal antibody (mAb)-based therapy of acute myeloid leukemia (AML). Lintuzumab, an unconjugated, humanized anti-CD33 mAb, has modest single-agent activity against AML but failed to improve patient outcomes in two randomized trials when combined with conventional chemotherapy. Gemtuzumab ozogamicin, an anti-CD33 mAb conjugated to the antitumor antibiotic calicheamicin, improved survival in a subset of AML patients when combined with standard chemotherapy, but safety concerns led to US marketing withdrawal. The activity of these agents confirms that CD33 remains a viable therapeutic target for AML. Strategies to improve the results of mAb-based therapies for AML include antibody engineering to enhance effector function, use of alternative drugs and chemical linkers to develop safer and more effective drug conjugates, and radioimmunotherapeutic approaches.
authors: Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. jurcicj@mskcc.org
authors: Joseph G
authors: JG
authors: Jurcic
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000079982:Gemtuzumab; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab; C477390:lintuzumab