Characterization and receptor specific toxicity of two diphtheria toxin‐related interleukin‐3 fusion proteins DAB389–mIL‐3 and DAB389–(Gly4Ser)2‐mIL‐3

We have constructed two fusion proteins, DAB389–mIL‐3 and DAB389‐(Gly4Ser)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. DAB389–(Gly4Ser)2‐mIL‐3 was up to 5 times more toxic than DAB389–mIL‐3, depending on the cell line (0.8×10−10 M