Chaperonin 10 immunosuppression

Abstract

The invention is directed to the use of cpn10 in transplantation and particularly to treatment and/or prevention of graft versus host disease. The invention provides a method of administration of cpn10 to a donor and/or recipient animal or cells, tissues or organs derived from the donor, although in a particularly advantageous form treatment of both the donor and recipient animal. The method may further include the administration to the donor and/or recipient animal at least one other immunosuppressive agent to prevent or alleviate graft versus host disease.

1 . A method of therapeutically or prophylactically treating graft versus host disease (GVHD), said method comprising:
 (i) administering a pharmaceutically-effective amount of chaperonin 10 (cpn10) or a derivative of cpn10 to a donor animal or cell, organ or tissue obtained therefrom; and   (ii) administering to a recipient animal a pharmaceutically-effective amount of cpn10 or a derivative of cpn10, to thereby delay, ameliorate, suppress or otherwise reduce one or more symptoms of GVHD following transplantation of the one or more donor animal cells, tissues or organs to the recipient animal.   
     
     
         2 . The method of  claim 1  wherein a pharmaceutically-effective amount of chaperonin 10 or a derivative of cpn10 is administered to said recipient animal both before and after step (ii). 
     
     
         3 . The method of  claim 1  wherein a pharmaceutically-effective amount of cpn10 or a derivative of cpn10 is administered to the donor and recipient animals for no more than 7 days prior to step (ii). 
     
     
         4 . The method of  claim 1  wherein a pharmaceutically-effective amount of cpn10 or a derivative of cpn10 is administered to the donor and recipient animals for 2 to 5 days prior to step (ii). 
     
     
         5 . The method of  claim 1  wherein a pharmaceutically-effective amount of cpn10 or a derivative of cpn10 is administered to the recipient animal for no more than 90 days after step (ii). 
     
     
         6 . The method of  claim 5  wherein a pharmaceutically-effective amount of cpn10 or a derivative of cpn10 is administered to the recipient animal for no more than 60 days after step (ii). 
     
     
         7 . The method of  claim 6  wherein a pharmaceutically-effective amount of cpn10 or a derivative of cpn10 is administered to the recipient animal for 10 to 30 days after step (ii). 
     
     
         8 . The method of  claim 1  wherein said cpn10 protein has an amino acid sequence set forth in  FIG. 1  (SEQ ID NO: 1). 
     
     
         9 . The method of  claim 1  wherein the pharmaceutically-effective amount of cpn10 or derivative of cpn10 administered to an animal is within the range 0.1-100 mg per kg body weight. 
     
     
         10 . The method of  claim 9  wherein the pharmaceutically-effective amount of cpn10 or derivative of cpn10 administered to an animal is within the range 0.1-10 mg per kg body weight. 
     
     
         11 . The method of  claim 1  wherein the cell, tissue or organ is, or is derived from, bone marrow. 
     
     
         12 . The method of  claim 1  wherein said animal is a mammal. 
     
     
         13 . The method of  claim 12  wherein said mammal is a human. 
     
     
         14 . The method of  claim 1  further comprising administering to said donor animal and/or said recipient animal at least one other immunosuppressive agent selected from the group consisting of cyclosporin, tacrolimus, sirolimus, mycophenolate mofetil, and methotrexate. 
     
     
         15 . The method of  claim 1  further comprising administering to said donor animal and/or recipient animal a steroid. 
     
     
         16 . A method of inhibiting, suppressing or otherwise reducing TNFα production in an animal , said method comprising administering to said animal a pharmaceutically-effective amount of cpn10 or derivative of cpn10 to thereby inhibit, suppress or otherwise reduce production of TNFα in said animal. 
     
     
         17 . The method of  claim 16  wherein said method induces, augments or otherwise increases IL-10 production. 
     
     
         18 . The method of  claim 16  wherein said animal is a mammal. 
     
     
         19 . The method of  claim 18  wherein said mammal is a human. 
     
     
         20 . An isolated polypeptide comprising the amino acid sequence set forth in  FIG. 1  (SEQ ID NO: 1).