| 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. |
| Keywords: |
unclassified drug; acute granulocytic leukemia; leukemia, myeloid, acute; fludarabine; review; placebo; drug safety; antineoplastic agents; cytarabine; methodology; antineoplastic agent; low drug dose; etoposide; monoclonal antibody; fever; immunology; myelodysplastic syndrome; rigor; iodine 131; drug mechanism; minimal residual disease; mitoxantrone; daunorubicin; promyelocytic leukemia; idarubicin; antigens, cd; drug half life; radioimmunotherapy; granulocyte colony stimulating factor; leukocyte antigen; therapy; cd33 antigen; gemtuzumab ozogamicin; differentiation antigen; antigens, differentiation, myelomonocytic; antibody engineering; acute promyelocytic leukemia; acute myelogenous leukemia; aminoglycoside; aminoglycosides; yttrium 90; actinium 225; astatine 211; bismuth 213; radium 223; acute myeloid leukemia; lintuzumab; bismuth 212; rhenium 188; gemtuzumab; combined chemotherapy; antibodies, monoclonal, humanized; copper 67; lead 212; cd33; patient selection .radioimmunotherapy
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