Abstract
We have constructed two fusion proteins, DAB 389–mIL-3 and DAB 389-(Gly 4Ser) 2–mIL-3, in which the receptor-binding domain of diphtheria toxin is replaced by mouse interleukin-3 (IL-3). Cytotoxic activity of the fusion toxins was observed on three out of six cell lines assayed. This toxicity was mediated through binding to the IL-3 receptor as it was inhibited in a dose-dependent manner with murine IL-3 or anti-IL-3 neutralizing antibodies. DAB 389–(Gly 4Ser) 2-mIL-3 was up to 5 times more toxic than DAB 389–mIL-3, depending on the cell line (0.8×10 −10 M<IC 50<3×10 −10 M). These proteins can be used for the detection of IL-3 receptors on mouse cells and should allow for the selective elimination of IL-3 receptor-positive pluripotent hematopoietic stem cells prior to bone marrow transplantation.
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