Methods and compositions based on diphtheria toxin-interleukin-3 conjugates

摘要

The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and/or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.

主权项

1. A method for inhibiting cancer cells in a human diagnosed with plasmacytoid dendritic cell cancer, comprising administering to said human an effective amount of a pharmaceutical composition comprising a human interleukin 3 (IL-3)-diphtheria toxin conjugate, wherein said conjugate is administered at a dose greater than 4 μg/kg to about 12.5 μg/kg, and wherein said method results in inhibition of the growth of plasmacytoid dendritic cell cancer cells.