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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1244-1247.
Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-02-002915.
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NEOPLASIA
Brief Report
Continuous delivery of human type I interferons ( /ß) has significant activity against acute myeloid leukemia cells in vitro and in a xenograft model
Reuben Benjamin1,
Asim Khwaja1,
Nalini Singh1,
Jenny McIntosh1,
Anthony Meager2,
Meenu Wadhwa2,
Christian Streck3,
Catherine Ng3,
Andrew M. Davidoff3, and
Amit C. Nathwani1,4
1 Department of Haematology, University College London, United Kingdom;
2 Division of Immunology and Endocrinology, National Institute for Biological Standards and Control, Herts, United Kingdom;
3 Division of Experimental Hematology and Department of Surgery, St Jude Children's Research Hospital, Memphis, TN;
4 National Blood Service, London, United Kingdom
In this study, we focused primarily on the antileukemic activity of interferon-ß (IFN-ß) in a murine xenograft model of acute myeloid leukemia (AML). Bolus administration of recombinant IFN-ß via the subcutaneous or intravenous route failed to show efficacy in mice injected with AML cells despite achieving peak plasma IFN-ß levels of more than 200 IU/mL. In contrast, stable expression of IFN-ß following adeno-associated virus (AAV) vector–mediated gene transfer resulted in significant antileukemic activity against primary AML cells derived from patients with poor prognostic markers. An almost linear relationship was observed with stable plasma levels of IFN-ß and antileukemic activity in mice. Even levels below 10 IU/mL were able to reduce tumor load by 50-fold when compared with control animals. These levels of IFN-ß are likely to be nontoxic in humans. Therefore, approaches capable of maintaining stable plasma levels of IFN-ß merit further clinical evaluation in patients with AML.
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