Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25.
Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 ((211)At)-labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25. Either a single dose of 12 microCi (0.444 MBq) (211)At-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 microg weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin (beta(2)mu) and by prolonged survival of leukemia-bearing mice compared with the control groups (P < .001). The combination of 2 agents enhanced the antitumor effect when compared with groups treated with 12 microCi (0.444 MBq) of (211)At-7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific antibody (211)At-11F11-treated group. In contrast, 91% of mice in the combination group survived through day 94. These results that demonstrate a significantly improved therapeutic efficacy by combining (211)At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL.
Metabolism Branch, NCI, NIH, Bldg 10, Room 4N115, 10 Center Drive, Bethesda, MD 20892-1374, USA.
Zhuo
Z
Zhang
Meili
M
Zhang
Kayhan
K
Garmestani
Vladimir S
VS
Talanov
Paul S
PS
Plascjak
Barbara
B
Beck
Carolyn
C
Goldman
Martin W
MW
Brechbiel
Thomas A
TA
Waldmann
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001246:Astatine / Q000627:therapeutic use; D000077561:Daclizumab; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000939:Epitopes; D007074:Immunoglobulin G / Q000627:therapeutic use; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D000077561:Daclizumab; D001246:Astatine