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 Blood, 1 August 2006, Vol. 108, No. 3, pp. 1007-1012.
Prepublished online as a Blood First Edition Paper on March 28, 2006; DOI 10.1182/blood-2005-11-4757.

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NEOPLASIA

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

Zhuo Zhang, Meili Zhang, Kayhan Garmestani, Vladimir S. Talanov, Paul S. Plascjak, Barbara Beck, Carolyn Goldman, Martin W. Brechbiel, and Thomas A. Waldmann

From the Metabolism Branch and the Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD; and Clinical Center, National Institutes of Health, Bethesda, MD.

Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 (211At)–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 µCi (0.444 MBq) 211At-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 µg weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin (beta2µ) 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 µCi (0.444 MBq) of 211At-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 211At-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 211At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL.


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 Proc. Natl. Acad. Sci. USAHome page
M. Zhang, Z. Yao, H. Patel, K. Garmestani, Z. Zhang, V. S. Talanov, P. S. Plascjak, C. K. Goldman, J. E. Janik, M. W. Brechbiel, et al.
Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1
PNAS, May 15, 2007; 104(20): 8444 - 8448.
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