Dpep-1 binding agents and methods of use

Abstract

Pharmaceutical compositions and methods of their use are provided for reducing inflammation in a subject, blocking leukocyte recruitment, inhibiting tumor metastasis, treating sepsis and preventing/reducing acute kidney injury.

1 .- 7 . (canceled) 
     
     
         8 . A method of treating or preventing a disorder in a human subject in need thereof, comprising administering to the subject an effective amount of an isolated DPEP-1 binding peptide, wherein the isolated DPEP-1 binding peptide comprises a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7. 
     
     
         9 . The method of  claim 8 , wherein the disorder is selected from the group consisting of acute kidney injury, sepsis and tumor metastasis. 
     
     
         10 . The method of  claim 8 , wherein the disorder is selected from the group consisting of inflammation and ischemia-reperfusion injury. 
     
     
         11 . The method of  claim 10 , wherein the ischemia-reperfusion injury is associated with harvesting donor organs for transplantation. 
     
     
         12 .- 14 . (canceled) 
     
     
         15 . The method of  claim 8 , wherein the peptide further comprises at least 1, 2, 3, 4, or 5 amino acid residues at the N-terminus. 
     
     
         16 . The method of  claim 8 , wherein the peptide comprises one or more amino acids selected from the group consisting of D-amino acids, modified amino acids, amino acid analogs or combinations thereof. 
     
     
         17 . The method of  claim 15 , wherein the modified amino acids comprise a modification selected from the group consisting of methylation, amidation, acetylation. 
     
     
         18 .- 22 . (canceled) 
     
     
         23 . The method of  claim 8 , wherein the disorder is associated with inflammation caused by ischemia/reperfusion injury to a tissue or organ. 
     
     
         24 . The methods of  claim 8 , wherein the disorder is associated with inflammation caused by arthritis, kidney failure, lupus, asthma, psoriasis, pancreatitis, allergy, fibrosis, surgical complications, anemia, fibromyalgia, cancer, Alzheimer's disease, congestive heart failure, stroke, aortic valve stenosis, arteriosclerosis, osteoporosis, Parkinson's disease, infection (sepsis), inflammatory bowel disease, or multiple sclerosis. 
     
     
         25 . A method of preventing, limiting or treating ischemia reperfusion injury in a subject, comprising (1) identifying a subject that has undergone an ischemic event, or in which an ischemic event is imminent or is at risk for having an ischemic event, and (2) administering a therapeutically effective or prophylactically effective amount of an isolated DPEP-1 binding peptide, wherein the isolated DPEP-1 binding peptide comprises a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7. 
     
     
         26 . The method of  claim 25 , wherein the isolated DPEP-1 binding peptide is administered until symptoms of ischemia-reperfusion injury are reduced or ameliorated. 
     
     
         27 . The method of  claim 25 , wherein the isolated DPEP-1 binding peptide is administered at a dosage between about 0.01 mg/kg to 100 mg/kg. 
     
     
         28 . A method of reducing or preventing acute kidney injury in a subject comprising administering an effective amount of a composition that binds to DPEP-1, wherein the composition that binds DPEP-1 is an isolated DPEP-1 binding peptide comprising a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, and SEQ ID NO:7. 
     
     
         29 . The method of  claim 28 , further comprising identifying a subject in need of treatment through diagnostic tests to determine a need for reduction or prevention of acute kidney injury. 
     
     
         30 . The method of  claim 28 , wherein the acute kidney injury is a result of sepsis, ischemia reperfusion, toxin-induced kidney injury or contrast-induced kidney injury.