SEARCH:   Advanced

Blood, 1 May 2008, Vol. 111, No. 9, pp. 4813-4816. Prepublished online as a Blood First Edition Paper on March 7, 2008; DOI 10.1182/blood-2008-01-133785. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-133785v1 111/9/4813    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Walter, R. B. Articles by Pagel, J. M. PubMed PubMed Citation Articles by Walter, R. B. Articles by Pagel, J. M. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report Simultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts Roland B. Walter1,2, Kelli M. Boyle1, Frederick R. Appelbaum1,3, Irwin D. Bernstein1,4, and John M. Pagel1,3 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Department of Medicine, Division of Hematology; 3 Department of Medicine, Division of Medical Oncology; and 4 Department of Pediatrics, University of Washington, Seattle Targeting CD33 or CD45 is currently exploited for immunotherapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO), an immunoconjugate of an anti-CD33 antibody that facilitates cellular uptake of a toxic calicheamicin-1 derivative, induces complete remissions in a subset of patients with AML. We herein tested whether simultaneous targeting of CD45 could improve GO cytotoxicity against AML cell lines and primary AML cells. We found that the anti-CD45 antibody, BC8, dose-dependently increased cytotoxicity induced by GO, and, to a lesser degree, free calicheamicin-1. BC8 promoted CD33 endocytosis, suggesting that its effect on GO cytotoxicity may be, at least partly, due to increased uptake and intracellular GO availability. Finally, compared with either agent alone, BC8 combined with GO resulted in marked tumor growth inhibition and superior survival rates of mice bearing human AML xenografts. These data suggest that further study of this antibody combination for clinical use in AML is warranted. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020