Disease-Associated Antigens and Methods of Use Thereof

Abstract

The present disclosure provides synthetic antibodies specific for a disease-associated antigen, and methods of using the antibodies in disease therapy. The present disclosure further provides diagnostic assays involving detecting the presence and/or level in biological sample of an antibody specific for a disease-associated antigen.

1 . A synthetic prostate cancer-associated polypeptide antigen, wherein the antigen comprises a polypeptide comprising an amino acid sequence having at least about 85% amino acid sequence identity to the amino acid sequence set forth in one of SEQ ID NOs: 1-42 and 108-147. 
     
     
         2 . The antigen of  claim 1 , wherein the polypeptide comprises an amino acid sequence that differs by at least one amino acid from the amino acid sequence set forth in one of SEQ ID NOs: 1-42 and 108-147. 
     
     
         3 . The antigen of  claim 1 , wherein the polypeptide has a length of from 6 amino acids to about 200 amino acids. 
     
     
         4 . The antigen of  claim 1 , wherein the polypeptide is multimerized. 
     
     
         5 . An immunogenic composition comprising:
 a) an antigen according to  claim 1 ; and   b) an adjuvant.   
     
     
         6 . The composition of  claim 5 , wherein the adjuvant comprises aluminum hydroxide, MF59, or monophosphoryl lipid A. 
     
     
         7 . The composition of  claim 5 , wherein the composition is formulated for parenteral administration. 
     
     
         8 . The composition of  claim 5 , wherein the composition is formulated for administration to a mucosal tissue. 
     
     
         9 . A method of determining the likelihood that an individual having prostate cancer will exhibit a clinically beneficial response to treatment with an immunomodulatory treatment regimen, the method comprising detecting in a biological sample obtained from the individual a level of antibody specific for one or more prostate cancer-associated antigens selected from a polypeptide of any one of SEQ ID NOs: 1-42 and 108-147, wherein a level of antibody that is at least about 25% higher than a control level of the antibody indicates that the individual is likely to exhibit a clinically beneficial response to the treatment. 
     
     
         10 . The method of  claim 9 , wherein the immunomodulatory treatment regimen comprises administering an immunomodulatory agent, administering a radiation treatment, or administering a hormonal therapy. 
     
     
         11 . The method of  claim 9 , wherein the immunomodulatory treatment regimen comprises administering an immunomodulatory agent, and wherein the immunomodulatory agent comprises a monoclonal antibody. 
     
     
         12 . The method of  claim 9 , wherein the immunomodulatory treatment regimen comprises administering an immunomodulatory agent, and wherein the immunomodulatory agent comprises an immunomodulatory cytokine. 
     
     
         13 . A monoclonal antibody specific for an antigen according to  claim 1 . 
     
     
         14 . The monoclonal antibody of  claim 13 , wherein the antibody is humanized. 
     
     
         15 . A synthetic Systemic Lupus Erythematosus (SLE)-associated polypeptide antigen, wherein the antigen comprises a polypeptide comprising an amino acid sequence having at least about 85% amino acid sequence identity to the amino acid sequence set forth in one of SEQ ID NOs: 43-85, 148, and 149. 
     
     
         16 . The antigen of  claim 15 , wherein the polypeptide comprises an amino acid sequence that differs by at least one amino acid from the amino acid sequence set forth in one of SEQ ID NOs: 43-85, 148, and 149. 
     
     
         17 . The antigen of  claim 15 , wherein the polypeptide has a length of from 6 amino acids to about 200 amino acids. 
     
     
         18 . The antigen of  claim 15 , wherein the polypeptide is multimerized. 
     
     
         19 . A method of diagnosing an individual as having Systemic Lupus Erythematosus (SLE), the method comprising detecting in a biological sample obtained from the individual a level of antibody specific for an SLE-associated polypeptide antigen selected from a polypeptide of any one of SEQ ID NOs: 43-85, 148, and 149, wherein a level of antibody greater than a level of antibody specific for the SLE-associated polypeptide antigen from a control individual is indicative of SLE. 
     
     
         20 . A method of assessing whether an individual is at risk of developing Systemic Lupus Erythematosus (SLE), the method comprising detecting in a biological sample obtained from the individual a level of antibody specific for an SLE-associated polypeptide antigen selected from a polypeptide of any one of SEQ ID NOs: 43-85, 148, and 149, wherein a level of antibody greater than a level of antibody specific for the SLE-associated polypeptide antigen from a control individual indicates that the individual is at risk for developing type 1 insulin dependent diabetes mellitus. 
     
     
         21 . A synthetic type 1 insulin dependent diabetes mellitus-associated polypeptide antigen, wherein the antigen comprises a polypeptide comprising an amino acid sequence having at least about 85% amino acid sequence identity to the amino acid sequence set forth in one of SEQ ID NOs: 86-107 and 150-155. 
     
     
         22 . The antigen of  claim 21 , wherein the polypeptide comprises an amino acid sequence that differs by at least one amino acid from the amino acid sequence set forth in one of SEQ ID NOs: 86-107 and 150-155. 
     
     
         23 . The antigen of  claim 21 , wherein the polypeptide has a length of from 6 amino acids to about 200 amino acids. 
     
     
         24 . The antigen of  claim 21 , wherein the polypeptide is multimerized. 
     
     
         25 . A method of diagnosing an individual as having type 1 insulin dependent diabetes mellitus, the method comprising detecting in a biological sample obtained from the individual a level of antibody specific for a type 1 diabetes-associated polypeptide antigen selected from a polypeptide of any one of SEQ ID NOs: 86-107 and 150-155, wherein a level of antibody greater than a level of antibody specific for the type 1 diabetes-associated polypeptide antigen from a control individual is indicative of type 1 insulin dependent diabetes mellitus. 
     
     
         26 . A method of assessing whether an individual is at risk of developing type 1 insulin dependent diabetes mellitus, the method comprising detecting in a biological sample obtained from the individual a level of antibody specific for a type 1 diabetes-associated polypeptide antigen selected from a polypeptide of any one of SEQ ID NOs: 86-107 and 150-155, wherein a level of antibody greater than a level of antibody specific for the type 1 diabetes-associated polypeptide antigen from a control individual indicates that the individual is at risk for developing type 1 insulin dependent diabetes mellitus.