Method of treating or ameliorating a pathogenic infection by administering an interleukin-2/TGF-β receptor fusion polypeptide
Provided are multi-functional and multi-valent fusion polypeptides comprising an interleukin polypeptide and two or more TGFβ ligand-binding polypeptides. The compositions and methods provided herein are useful in the application of treating and/or preventing pathogenic infections.
1. A method of treating or ameliorating a pathogenic infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a fusion polypeptide comprising:
an interleukin-2 (IL 2) polypeptide or a fragment thereof comprising an IL-2 receptor binding domain;
a first soluble TGFβ receptor II (sTβRII) polypeptide or a fragment thereof comprising a ligand binding domain; and
a second soluble TGFβ receptor II (sTβRII) polypeptide or a fragment thereof comprising a ligand binding domain,
thereby treating or ameliorating the pathogenic infection in the subject.
2. The method of claim 1 , wherein the pathogenic infection comprises an intracellular pathogen.
3. The method of claim 1 , wherein the IL-2 polypeptide comprises SEQ ID NO: 2 or 3, or a fragment thereof comprising an IL-2 receptor binding domain.
4. The method of claim 1 , wherein the IL-2 polypeptide comprises an amino acid sequence having greater than about 80% sequence identity to SEQ ID NO: 2.
5. The method of claim 1 , wherein the first sTβRII polypeptide, the second sTβRII polypeptide, or both, comprise amino acid sequence having greater than about 80% sequence identity to SEQ ID NO: 8 or SEQ ID NO: 9.
6. The method of claim 1 , wherein the first sTβRII polypeptide, the second sTβRII polypeptide, or both, bind a TGFβ1 polypeptide, a TGFβ2 polypeptide, a TGFβ3 polypeptide, or any combination thereof.
7. The method of claim 1 , wherein the first sTβRII polypeptide and the second sTβRII polypeptide bind a TGFβ1 polypeptide.
8. The method of claim 1 , wherein the fusion polypeptide comprises an amino acid sequence having at least about 80% sequence identity to any one of SEQ ID NOs: 10-25.
9. The method of claim 1 , wherein the pathogenic infection is an intracellular bacterial infection.
10. The method of claim 1 , wherein the pathogenic infection is a viral infection.
11. The method of claim 1 , wherein the administering comprises administering the fusion polypeptide to the subject by systemic administration.
12. The method of claim 1 , wherein the administering comprises administering the fusion polypeptide to the subject by intravenous administration.
13. The method of claim 1 , wherein the administering comprises administering a pharmaceutical composition comprising the fusion polypeptide to the subject.
14. The method of claim 13 , wherein the pharmaceutical composition comprises one or more pharmaceutically acceptable excipients, carriers, diluents, or any combination thereof.
15. The method of claim 1 , wherein the subject is a human.