CD 33 as a target of therapy in acute myeloid leukemia: current status and future perspectives.
CD 33 is a myeloid cell surface antigen that is expressed on blast cells in acute myeloid leukemia (AML) in a majority of all patients regardless of age or subtype of disease. The antigen is also expressed on leukemic stem cells in many cases, but is not expressed on normal hematopoietic stem cells. In an attempt to improve therapy in AML, a CD 33-targeted drug has been developed. The drug, gemtucumab ozogamicin (GO; Mylotarg), consists of a humanized CD 33 antibody (hP 67.6), a pH-dependent linker, and a highly potent chemotherapy agent, calicheamicin 1,2,-dimethyl hydrazine dichloride. Based on its clinical activity, GO has been approved for application in chemotherapy-refractory AML in various countries and is effective as a mono-substance as well as in combination with conventional chemotherapy. However, despite high efficacy and a certain specificity for leukemic (as opposed to normal) stem cells, the drug does not work in all patients, and can produce significant side-effects, including veno-occlusive disease (VOD), especially in patients who undergo stem cell transplantation. These side-effects have to be balanced against the benefit of GO therapy in patients with relapsed or refractory AML.
Sperr
Wolfgang R
WR
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
Florian
Stefan
S
Hauswirth
Alexander W
AW
Valent
Peter
P
D000208:Acute Disease; D000617:Aminoglycosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D053281:Enediynes; D000079982:Gemtuzumab; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics; D063268:Sialic Acid Binding Ig-like Lectin 3
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D053281:Enediynes; D063268:Sialic Acid Binding Ig-like Lectin 3; C509660:calicheamicin 1,2,-dimethyl hydrazine dichloride; D000079982:Gemtuzumab