title: Antileukemic effect of daclizumab in CD25 high-expressing leukemias and impact of tumor burden on antibody dosing.
abstract: Humanized anti-CD25 antibody, daclizumab, was applied in a pilot study of 10 patients with CD25(+) leukemias and pharmacokinetic/pharmacodynamic properties were characterized. Two widely held concepts - tumor sink accelerating pharmacokinetics and higher antigen expression correlating with target cell clearance - were supported by this first systematic evaluation of these questions with actual human clinical data. A flexi-dosing regimen was validated for maintaining target drug levels in vivo with a wide range of tumor burdens. Daclizumab induced clearance of peripheral leukemic cells when highly positive for CD25, but durable responses were not obtained. If daclizumab will have a role in antileukemic therapy, it may be in minimal disease settings or as a component of a combination regimen, but only when CD25 expression is high.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: H B
authors.initials: HB
authors.lastname: Koon
authors.forename: P
authors.initials: P
authors.lastname: Severy
authors.forename: D S
authors.initials: DS
authors.lastname: Hagg
authors.forename: K
authors.initials: K
authors.lastname: Butler
authors.forename: T
authors.initials: T
authors.lastname: Hill
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
authors.forename: T A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: R P
authors.initials: RP
authors.lastname: Junghans
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D007205:Indium Radioisotopes; D007938:Leukemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011877:Radionuclide Imaging; D015375:Receptors, Interleukin-2 / Q000032:analysis*
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D015375:Receptors, Interleukin-2; D000077561:Daclizumab