Method of treatment

Abstract

The present invention relates generally to the field of immunomodulation. Taught herein is an agent for inhibiting immunostimulation mediated by a Toll-like receptor useful in the treatment of viral and microbial pathogenesis, diseases involving elements of autoimmunity and inflammation as well as cancer. The agent antagonizes disulfide bond formation between C98 and C475 of Toll-like receptor 7 (TLR7) thereby preventing TLR7 activation. Pharmaceutical compositions are also enabled herein.

What is claimed: 
     
         1 . A peptide of up to 190 amino acids in length, comprising the amino acid sequence DX 1 RCNCX 2 PX 3 X 4  (SEQ ID NO: 27) wherein:
 X 1  is L, F or M;   X 2  is V or I;   X 3  is V or I or A or P; and   X 4  is P or L or K or R.   
     
     
         2 . The peptide of  claim 1 , wherein the peptide comprises the amino acid sequence DFRCNCVPIP (SEQ ID NO: 26). 
     
     
         3 . The peptide of  claim 1 , wherein the peptide comprises the amino acid sequence DLRCNCVPVL (SEQ ID NO: 1). 
     
     
         4 . The peptide of  claim 1 , wherein the peptide further comprises a moiety attached to the N-terminal or C-terminal end of the peptide which enables uptake of the peptide into the cell. 
     
     
         5 . The peptide of  claim 4 , wherein the moiety is a hydrophilic peptide, an amphiphilic peptide, a peptide with a periodic amino acid sequence or a conjugate with cholestanol. 
     
     
         6 . The peptide of  claim 4 , wherein the moiety is a hydrophilic peptide selected from the group consisting of TAT (SEQ ID NO: 2), SynB1 (SEQ ID NO: 3), SynB3 (SEQ ID NO: 4), PTD-4 (SEQ ID NO: 5), PTD-5 (SEQ ID NO: 6), FHV coat (SEQ ID NO: 7), BMV Gag-(7-25) (SEQ ID NO: 8), HTLV-II Rex-(4-16) (SEQ ID NO: 9), D-Tat (SEQ ID NO: 10) and R9-Tat (SEQ ID NO: 11). 
     
     
         7 . The peptide of  claim 4 , wherein the moiety is an amphiphilic peptide selected from the group consisting of Transportan chimera (SEQ ID NO: 12), MAP (SEQ ID NO: 13), SBP (SEQ ID NO: 14), FBP (SEQ ID NO: 15), MPG [MPGac] (SEQ ID NO: 16), MPG (ΔNLS) (SEQ ID NO: 17), Pep-1 (SEQ ID NO: 18) and Pep-2 (SEQ ID NO: 19). 
     
     
         8 . The peptide of  claim 4 , wherein the moiety is a periodic amino acid sequence comprising a polyarginine or a polylysine sequence. 
     
     
         9 . The peptide of  claim 1 , wherein the peptide is up to 100 amino acids in length. 
     
     
         10 . The peptide of  claim 1 , wherein the peptide is up to 40 amino acids in length. 
     
     
         11 . A pharmaceutical composition comprising the peptide of  claim 1  and one or more pharmaceutical carriers, excipients and/or diluents. 
     
     
         12 . A method for inhibiting TLR7-mediated immunostimulatory activity in a TLR7-expressing cell, the method comprising contacting the cell with the peptide of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the cell is of a subject with an autoimmune disease, a viral pathogenesis, a microbial pathogenesis, an inflammation or a cancer. 
     
     
         14 . The method of  claim 13 , wherein the cell is of a subject with a viral pathogenesis. 
     
     
         15 . A method for inhibiting TLR7-mediated immunostimulatory activity in a TLR7-expressing cell in a subject, the method comprising administering to the subject an effective amount of the peptide of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein the subject has an autoimmune disease, a viral pathogenesis, a microbial pathogenesis, an inflammation or a cancer. 
     
     
         17 . The method of  claim 16 , wherein the subject has a viral pathogenesis.