Cd40 targeted peptides and uses thereof

Abstract

The present disclosure is related to compositions comprising peptides that bind CD40 and methods of use in inhibiting interaction of CD40 and CD154 and inducing immunosuppression. Provided herein are methods of transplantation and methods of inhibiting donor specific immune response. Also provided herein are methods of treatment for autoimmune diseases, inflammatory diseases and cancer.

1 . A method of treating inflammation in a subject, the method comprising:
 administering to the subject an effective amount of a pharmaceutical composition that comprises:
 an isolated peptide that comprises an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-6 or SEQ ID NOs: 8-17, as determined by BLAST algorithm; and 
 a pharmaceutically acceptable excipient, carrier, or diluent, 
 wherein said administering is in an amount sufficient to result in a reduction of B cell activation in said subject as compared to the B cell activation in said subject prior to said administering, thereby treating the inflammation in the subject. 
   
     
     
         2 . The method of  claim 1 , wherein said isolated peptide comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1-6 or SEQ ID NOs: 8-17. 
     
     
         3 . The method of  claim 1 , wherein said isolated peptide further comprises at least one modification, wherein said at least one modification is a chemical modification, or a post-translational modification. 
     
     
         4 . The method of  claim 3 , wherein said chemical modification is selected from a group consisting of ubiquitination, pegylation, lipidation, glycosylation, alkylation, or thiolation. 
     
     
         5 . The method of  claim 3 , wherein said post-translational modification is an acetylation, acylation, ADP-ribosylation, amidation, carboxylation, hydroxylation, disulfide bond formation, glycosylation, phosphorylation, proteolytic processing, sulfation, methylation, acyl lipidation, prenylation, methylation, or myristoylation. 
     
     
         6 . The method of  claim 1 , wherein said isolated peptide is cyclized. 
     
     
         7 . The method of  claim 1 , wherein said isolated peptide is further conjugated to a carrier polypeptide, a detectable agent, a peptide tag, a magnetic particle, a diagnostic agent, a therapeutic agent, a nanoparticle, or a combination thereof. 
     
     
         8 . The method of  claim 1 , wherein said isolated peptide is formulated in a liposome or a nanoparticle delivery system. 
     
     
         9 . The method of  claim 1 , wherein said isolated peptide inhibits binding of a CD40 protein to a CD154 protein. 
     
     
         10 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein said inflammation is associated with an autoimmune disease. 
     
     
         22 . A method of reducing proliferation of one or more of T cells and B cells in a subject, the method comprising:
 administering to the subject an effective amount of a pharmaceutical composition that comprises an isolated peptide that comprises an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-6 or SEQ ID NOs: 8-17, as determined by BLAST algorithm and a pharmaceutically acceptable excipient, carrier, or diluent,   wherein the pharmaceutical composition is administered in an amount sufficient to result in inhibition of proliferation of at least one of T cells and B cells in said subject as compared to inhibition of proliferation of T cells and B cells in said subject prior to said administering, thereby treating the inflammation in the subject.   
     
     
         23 . The method of  claim 22 , wherein said isolated peptide comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1-6 or SEQ ID NOs: 8-17. 
     
     
         24 . The method of  claim 22 , wherein said isolated peptide further comprises at least one modification, wherein said at least one modification is a chemical modification, or a post-translational modification. 
     
     
         25 . The method of  claim 22 , wherein said isolated peptide is cyclized. 
     
     
         26 . The method of  claim 22 , wherein said isolated peptide is formulated in a liposome or a nanoparticle delivery system. 
     
     
         27 . The method of  claim 22 , wherein said isolated peptide inhibits binding of a CD40 protein to a CD154 protein. 
     
     
         28 . A method of treating a neoplastic disease characterized by CD40 expression in a subject, the method comprising:
 administering to the subject an effective amount of a pharmaceutical composition that comprises an isolated peptide that comprises an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-6 or SEQ ID NOs: 8-17, as determined by BLAST algorithm and a pharmaceutically acceptable excipient, carrier, or diluent,   wherein the pharmaceutical composition is administered in an amount sufficient to result in a reduction of CD40 expression in said subject as compared to CD40 expression in said subject prior to said administering, thereby treating the neoplastic disease characterized by said CD40 expression in said subject.   
     
     
         29 . The method of  claim 28 , wherein the isolated peptide blocks CD40-CD40L signaling. 
     
     
         30 . The method of  claim 28 , wherein the neoplastic disease is a lymphoma, a myeloma or a carcinoma.