Blockade of ccl18 signaling via ccr6 as a therapeutic option in fibrotic diseases and cancer

Abstract

The present invention relates to an isolated soluble CCR6 receptor polypeptide capable of binding to CCL18 and/or CCL20 and to a method for quantifying the concentration of a soluble CCR6 receptor polypeptide in a liquid sample from a subject. The present invention also relates to a method for detecting and/or prognosticating an interstitial lung disease or a cancer in a subject by determining the level of a soluble CCR6 receptor polypeptide in a sample from said subject and further provides a pharmaceutical composition comprising a compound capable of inhibiting the activity and/or the expression of CCL18 or CCL20 for the treatment of said diseases. The present invention further relates to an isolated polypeptide capable of binding to and inhibiting the activity of the chemokine receptor CCR6 and to a method for identifying further inhibitors of CCR6 receptor activity. The present invention also relates to a method for detecting an interstitial lung disease or a cancer in a subject by determining the level of CCR6 gene expression in a sample from said subject and further provides pharmaceutical compositions comprising inhibitors of CCR6 receptor activity and/or expression for the treatment of said diseases.

1 - 22 . (canceled) 
     
     
         23 . A method of inhibiting CCR6 signaling in a subject, the method comprising:
 administering to the subject an isolated soluble CCR6 receptor polypeptide,   wherein the isolated soluble CCR6 receptor polypeptide comprises an amino acid sequence that exhibits at least 80% sequence identity to the sequence according to SEQ ID NO:1, or wherein the isolated soluble CCR6 receptor polypeptide comprises at least 40 consecutive amino acids of the sequence according to SEQ ID NO:1.   
     
     
         24 . The method of  claim 23 , wherein the isolated soluble CCR6 receptor polypeptide binds to CCL18 and/or CCL20. 
     
     
         25 . The method of  claim 23 , wherein the amino acid sequence exhibits at least 80% identity to the sequence according to SEQ ID NO:1 and comprises at least 40 consecutive amino acids of the sequence according to SEQ ID NO:1. 
     
     
         26 . The method of  claim 23 , wherein the amino acid sequence exhibits at least 85% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         27 . The method of  claim 23 , wherein the amino acid sequence exhibits at least 90% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         28 . The method of  claim 23 , wherein the amino acid sequence exhibits at least 93% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         29 . The method of  claim 23 , wherein the isolated soluble CCR6 receptor polypeptide comprises at least 45 consecutive amino acids of the sequence according to SEQ ID NO:1. 
     
     
         30 . The method of  claim 23 , wherein the amino acid sequence exhibits at least 95% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         31 . The method of  claim 23 , wherein the amino acid sequence exhibits at least 97% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         32 . The method of  claim 23 , wherein the amino acid sequence exhibits 100% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         33 . The method of  claim 23 , wherein the amino acid sequence comprises at least 48 amino acids which exhibits at least 80% identity to the sequence according to SEQ ID NO:1, or a fragment thereof, wherein said fragment has a length of at least 40 amino acids, and wherein the isolated soluble CCR6 receptor polypeptide binds to CCL18 and/or CCL20. 
     
     
         34 . The method of  claim 23 , wherein the amino acid sequence which exhibits at least 95% identity to the sequence according to SEQ ID NO:1, and wherein the isolated soluble CCR6 receptor polypeptide binds to CCL18 and/or CCL20. 
     
     
         35 . The method of  claim 23 , wherein CCR6 signaling is inhibited by at least 50%. 
     
     
         36 . The method of  claim 23 , wherein the subject is suffering from an interstitial lung disease or susceptible to suffering from an interstitial lung disease. 
     
     
         37 . The method of  claim 36 , wherein administration of an effective amount of an isolated soluble CCR6 receptor polypeptide to the subject treats and/or prevents the interstitial lung disease. 
     
     
         38 . A method of inhibiting CCR6 signaling in a subject to treat and/or prevent an interstitial lung disease in the subject, the method comprising:
 providing a compound comprising an isolated soluble CCR6 receptor polypeptide; and   administering to the subject an effective amount of an isolated soluble CCR6 receptor polypeptide,   wherein the isolated soluble CCR6 receptor polypeptide comprises an amino acid sequence that exhibits at least 95% sequence identity to the sequence according to SEQ ID NO:1, and   wherein the isolated soluble CCR6 receptor polypeptide binds to CCL18 and/or CCL20,   whereby the interstitial lung disease is treated and/or prevented in the subject.   
     
     
         39 . The method of  claim 38 , wherein the isolated soluble CCR6 receptor polypeptide comprises at least 45 consecutive amino acids of the sequence according to SEQ ID NO:1. 
     
     
         40 . The method of  claim 38 , wherein the amino acid sequence exhibits at least 99% sequence identity to the sequence according to SEQ ID NO:1. 
     
     
         41 . The method of  claim 38 , wherein the subject is a human subject. 
     
     
         42 . The method of  claim 38 , wherein the interstitial lung disease is selected from the group consisting of idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamtive interstitial pneumonia, acute interstitial pneumonia, and lymphocytic interstitial pneumonia.