Hsp60, hsp60 peptides and t cell vaccines for immunomodulation

Abstract

The present invention provides novel uses for peptide p277—positions 437-460 of human heat shock protein 60 (HSP60)—in modulation of immune responses and inflammatory diseases. The invention further provides novel uses for HSP60 and p277 in the treatment or prevention of hepatic disorders. The invention discloses methods for treating, preventing or ameliorating the symptoms of T cell mediated inflammatory and autoimmune disorders, including hepatic disorders, which comprise administering to a subject in need thereof a composition comprising as an active ingredient an effective quantity of a molecule selected from: HSP60, p277, fragments, analogs, homologs and derivatives thereof, and nucleic acids encoding same. Also disclosed are T cell vaccination methods for treating or preventing T cell mediated disorders.

1 . (canceled) 
     
     
         2 . A pharmaceutical composition comprising a first population of T cells cultured ex vivo in the presence of a second population of T cells, the second population of T cells being attenuated activated histocompatible T cells exposed ex vivo to a compound selected from a group consisting of: p277 (SEQ ID NO:1), p277(Val 6 Val 11 ) (SEQ ID NO:2), p277(Ser 6 Ser 11 ) (SEQ ID NO:3), analogs, variants, derivatives and salts thereof. 
     
     
         3 - 8 . (canceled) 
     
     
         9 . A method of treating hepatitis comprising administering to a subject in need thereof a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of an HSP60 fragment analog having an amino acid sequence set forth in SEQ ID NO: 2, and a pharmaceutically acceptable carrier or diluent. 
     
     
         10 - 14 . (canceled) 
     
     
         15 . The method of  claim 9 , wherein the compound is administered in the form of a pharmaceutical composition further comprising a pharmaceutically acceptable carrier or diluent. 
     
     
         16 . The method of  claim 15 , wherein the composition comprises a sustained release formulation. 
     
     
         17 . A method of treating or preventing liver damage comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of an HSP60 fragment analog having an amino acid sequence set forth in SEQ ID NO: 2, and a pharmaceutically acceptable carrier or diluent. 
     
     
         18 - 22 . (canceled) 
     
     
         23 . The method of  claim 17 , wherein the subject in need thereof is afflicted with a disease selected from: (i) viral hepatitis (ii) parasitic hepatitis (iii) autoimmune hepatitis (iv) primary biliary cirrhosis (v) alcoholic liver disease. 
     
     
         24 . The method of  claim 17 , wherein the compound is administered in the form of a pharmaceutical composition further comprising a pharmaceutically acceptable carrier or diluent. 
     
     
         25 . The method of  claim 24 , wherein the composition comprises a sustained release formulation. 
     
     
         26 - 56 . (canceled) 
     
     
         57 . A method of treating or preventing a T cell mediated pathology in a subject in need thereof, comprising administering the pharmaceutical composition according to  claim 2  to the subject in an amount sufficient to induce an anti-ergotypic response in said subject. 
     
     
         58 . The method of  claim 57 , wherein the first population of T cells was isolated from the subject or from a donor histocompatible with said subject. 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 57 , wherein the T cell mediated pathology is selected from the group consisting of: inflammatory diseases, autoimmune diseases, allergic diseases and Th1 mediated diseases. 
     
     
         61 - 62 . (canceled) 
     
     
         63 . The method of  claim 57  wherein the T cell mediated pathology is hepatitis or liver damage associated therewith. 
     
     
         64 . (canceled)