Compositions and methods for treating inflammation and fibrosis

Abstract

The present invention features compositions featuring agents that bind to denatured collagen and methods of using such agents to treat or prevent fibrosis or inflammation in a subject.

1 . A method of reducing fibrosis, inflammation, or inflammatory cell infiltration of a site in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent that binds denatured collagen type I-IV, wherein the agent is selected from the group consisting of: proteins, peptides, antibodies, aptamers, oligopeptides and small molecule inhibitors. 
     
     
         2 . The method of  claim 1 , wherein the agent reduces the infiltration of one or more types of inflammatory cells selected from the group consisting of: monocytes, macrophages, neutrophils, and mast cells to a site in said subject. 
     
     
         3 . (canceled) 
     
     
         4 . A method of preventing or reducing ultraviolet radiation damage, ionizing radiation damage, or chemotherapy damage to a cell, tissue, or organ, the method comprising administering to the subject a therapeutically effective amount of an agent that binds denatured collagen type I-IV, wherein the agent is selected from the group consisting of: proteins, peptides, antibodies, aptamers, oligopeptides and small molecule inhibitors. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the inflammatory cell is selected from the group consisting of: monocytes, macrophages, neutrophils, and mast cells. 
     
     
         7 . The method of  claim 1 , wherein the agent reduces inflammatory cell infiltration to a site. 
     
     
         8 . The method of  claim 1 , wherein the agent reduces adhesion to extracellular matrix or basement membrane. 
     
     
         9 . The method of  claim 1 , wherein the agent reduces fibroblast cell adhesion to denatured collagen type I-IV. 
     
     
         10 . The method of  claim 4 , wherein the agent is administered prior to, concurrent with, or subsequent to UVA radiation or ionizing radiation exposure or prior to chemotherapy. 
     
     
         11 . The method of  claim 1 , wherein the site is the site of a bio-implant. 
     
     
         12 . The method of  claim 1 , wherein the agent is an antibody. 
     
     
         13 . The method of  claim 11 , wherein the antibody is a monoclonal antibody. 
     
     
         14 . The method of  claim 11 , wherein the antibody is humanized. 
     
     
         15 . The method of  claim 1 , wherein the agent specifically binds to an epitope of denatured collagen type-IV. 
     
     
         16 . The method of  claim 11 , wherein the agent specifically binds to an epitope of anti-denatured collagen type-IV comprising GLGP (SEQ ID NO: 2), GLGPGP (SEQ ID NO: 3), or OGAKGLPGPOGPOGPY (SEQ ID NO: 1). 
     
     
         17 . The method of  claim 16 , wherein the agent is selected from the group consisting of: L-K-Q-N-G-G-N-F-S-L (SEQ ID NO: 4), L-G, S-L-K-Q-N-G-G-N-F-S-L (SEQ ID NO: 5), C-L-K-Q-N-G-G-N-F-S-L-G (SEQ ID NO: 6), S-L-K-Q-N-G-G-N-F-S-L-C (SEQ ID NO: 7) and K-G-G-C-L-K-Q-N-G-G-N-F-S-L-G-G-K (SEQ ID NO: 8). 
     
     
         18 . The method of  claim 1 , wherein the subject has a condition selected from the group consisting of pulmonary fibrosis, liver fibrosis, and kidney fibrosis. 
     
     
         19 . The method of  claim 1 , wherein the inflammation is associated with a tissue selected from the group consisting of pulmonary, liver, brain or kidney tissue. 
     
     
         20 . The method of  claim 1 , wherein the inflammation and/or fibrosis is associated with a condition selected from the group consisting of arthritis, arthrosclerosis, scleroderma, sarcoidosis, psoriasis, inflammatory eye diseases, ischemic and inflammatory cardiovascular diseases, and ischemic and inflammatory bowel diseases. 
     
     
         21 . A kit for use in reducing inflammatory cell infiltration into a site comprising an agent that binds denatured collagen type I-IV, and instructions for use. 
     
     
         22 . A kit for use in treating or preventing fibrosis or inflammation in a subject, the kit comprising an agent that binds denatured collagen type I-IV, and instructions for use.