IMR Press / FBL / Volume 18 / Issue 4 / DOI: 10.2741/4181

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin

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1 Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA, USA
2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
3 Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA
4 Department of Epidemiology, University of Washington, Seattle, WA, USA
Academic Editor:Arthur E. Frankel
Front. Biosci. (Landmark Ed) 2013, 18(4), 1311–1334; https://doi.org/10.2741/4181
Published: 1 June 2013
(This article belongs to the Special Issue Clinical antibody drug conjugates)
Abstract

Antibodies have created high expectations for effective yet tolerated therapeutics in acute myeloid leukemia (AML). Hitherto the most exploited target is CD33, a myeloid differentiation antigen found on AML blasts in most patients and, perhaps, leukemic stem cells in some. Treatment efforts have focused on conjugated antibodies, particularly gemtuzumab ozogamicin (GO), an anti-CD33 antibody carrying a toxic calicheamicin-γ1 derivative that, after intracellular hydrolytic release, induces DNA strand breaks, apoptosis, and cell death. Serving as paradigm for this strategy, GO was the first anti-cancer immunoconjugate to obtain regulatory approval in the U.S. While efficacious as monotherapy in acute promyelocytic leukemia (APL), GO alone induces remissions in less than 25- 35% of non-APL AML patients. However, emerging data from well controlled trials now indicate that GO improves survival for many non-APL AML patients, supporting the conclusion that CD33 is a clinically relevant target for some disease subsets. It is thus unfortunate that GO has become unavailable in many parts of the world, and the drug’s usefulness should be reconsidered and selected patients granted access to this immunoconjugate.

Keywords
AML
Antibody
Calicheamicin
CD33
Gemtuzumab ozogamicin
Immunoconjugate
Review
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