Continuous delivery of human type I interferons ( / ) has significant activity against acute myeloid leukemia cells in vitro and in a xenograft model

In this study, we focused primarily on the antileukemic activity of interferon(IFN) in a murine xenograft model of acute myeloid leukemia (AML). Bolus administration of recombinant IFNvia the subcutaneous or intravenous route failed to show efficacy in mice injected with AML cells despite achieving peak plasma IFNlevels of more than 200 IU/mL. In contrast, stable expression of IFNfollowing 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 IFNand 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 IFNare likely to be nontoxic in humans. Therefore, approaches capable of maintaining stable plasma levels of IFNmerit further clinical evaluation in patients with AML. (Blood. 2007;109:1244-1247)