Methods of treating an autoimmune disease with a human interleukin-3 (IL-3)-diphtheria toxin conjugate (DT-IL3)

A method of treating an autoimmune disease in a human subject, the method comprising reducing the number of plasmacytoid dendritic cells (pDCs) in the subject by administering a therapeutically effective dose of a human interleukin-3 (IL-3)-diphtheria toxin conjugate (DT-IL3) to the human subject,

• wherein the DT-IL3 comprises diphtheria toxin (DT) and interleukin-3 protein (IL-3), linked via a linker molecule, wherein:
• (a) the DT comprises an amino acid sequence having a sequence at least 98% identical to the amino acid sequence of SEQ ID NO:3, wherein the amino acid sequence at least 98% identical to the amino acid sequence of SEQ ID NO:
• 3 comprises at least two domains of DT comprising:
• (i) a catalytic domain comprising the sequence of amino acids 26-112 of SEQ ID NO:
• 1;
• and
• (ii) a translocation domain comprising amino acids 225-404 of SEQ ID NO:1, and
• (b) the IL-3 comprises an amino acid sequence having a sequence at least 95% identical to a mature IL-3 amino acid sequence having the amino acid sequence of SEQ ID NO:
• 2 without a signal peptide;
• wherein the human subject prior to treatment has an elevated expression of at least one type I IFN-inducible gene in the skin or peripheral blood as compared to a healthy human subject;
• and
• wherein the treatment reduces the level of at least one cytokine or chemokine selected from chemokine ligand 4 (CXCL4), CXCL9, CXCL10, one or more type I interferons (type I IFNs), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-8, regulated upon activation normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein 1α (MIP1α), MIP1β, and monocyte chemoattractant protein-1 (MCP1) in the human subject.