Methods for the treatment of graft-versus-host disease
Methods are disclosed for treating or preventing graft versus host disease in a subject. The methods include selecting a subject in need of treatment for graft versus host disease; and administering to the subject a therapeutically effective amount of a TLR5 agonist such as a flagellin polypeptide, or a polynucleotide encoding the flagellin, thereby treating or preventing graft versus host disease in the subject. Methods are also disclosed for reducing susceptibility to an opportunistic infection in a subject who is a bone marrow transplant recipient. The methods include selecting a subject who has had a bone marrow or hematopoietic stem cell transplant; and administering to the subject a therapeutically effective amount of a TLR5 agonist such as a flagellin polypeptide or a polynucleotide encoding the polypeptide, and administering to the subject an effective amount antigen of the opportunistic infection, thereby reducing the susceptibility to the opportunistic infection in the subject.
1. A method of treating or preventing graft versus host disease in a subject, comprising: selecting a subject in need of treatment for graft versus host disease; and administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a flagellin polypeptide or fragment thereof able to activate the toll-Like Receptor 5 (TLR5) pathway, thereby treating or preventing graft versus host disease in the subject.
2. The method of, claim 1 , wherein the subject in need of treatment for graft versus host disease has or will receive an allogeneic bone marrow or hematopoietic stem cell transplant.
3. The method of, claim 1 , wherein the flagellin polypeptide is administered concurrently with an allogeneic bone marrow or hematopoietic stem cell transplant.
4. The method of, claim 1 , wherein the flagellin polypeptide is administered following an allogeneic bone marrow or hematopoietic stem cell transplant.
5. The method of, claim 1 , wherein the flagellin polypeptide is administered prior to an allogeneic bone marrow or hematopoietic stem cell transplant.
6. The method of claim 1 , wherein the flagellin polypeptide comprises the N-terminal constant region and the C-terminal constant region.
7. The method of claim 1 , wherein the flagellin polypeptide-comprises at least 100 amino acids of the N-terminal amino acid sequence and at least 100 C-terminal amino acids of Salmonella typhimurium flagellin containing at most 20 amino acid substitutions.
8. The method of claim 7 , wherein the N-terminal amino acid sequence comprises the amino acid sequence of SEQ ID NO:3.
9. The method of claim 7 , wherein the C-terminal amino acid sequence comprises the amino acid sequence of SEQ ID NO:4.
10. The method of claim 1 , wherein the flagellin polypeptide comprises amino acids 78-129, amino acids 135-173, amino acids 394-444, or any combination thereof from SEQ ID NO:2.
11. The method of claim 1 , wherein the subject is human.
12. The method of claim 1 , wherein the flagellin polypeptide comprises the amino acid sequence of SEQ ID NO:1 or 2.
13. The method of claim 1 , wherein the flagellin polypeptide is CBLB502.
14. A method for reducing susceptibility to an opportunistic infection in a subject who is a bone marrow transplant recipient, comprising selecting a subject who has had an allogeneic bone marrow or hematopoietic stem cell transplant; and administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a flagellin polypeptide or fragment thereof able to activate the toll-Like Receptor 5 (TLR5) pathway; administering to the subject an effective amount of an antigen of the opportunistic infection; wherein the pharmaceutical composition and the antigen reduce the susceptibility to the opportunistic infection in the subject.