Compositions and methods for promoting tissue repair using heat shock proteins

Abstract

The invention relates to methods and compositions for the promotion of tissue repair. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, uncompleted or completed noncovalently with antigenic molecules, are disclosed. Therapeutic methods for administering the hsp-containing compositions are disclosed. The disclosed methods are useful for promoting repair of tissues that were disrupted by a variety of causes including trauma (e.g., surgery, injury or burns) or disease or disorder (e.g., atherosclerosis and multiple sclerosis).

What is claimed is:  
     
         1 . A method of promoting tissue repair in a mammal comprising administering to the mammal a composition comprising a purified complex of heat shock protein noncovalently bound to a molecule.  
     
     
         2 . A method of promoting tissue repair in a mammal comprising administering to the mammal a composition comprising a purified heat shock protein.  
     
     
         3 . The composition of  claim 2  wherein the heat shock protein is substantially free of complexed molecules.  
     
     
         4 . The method of  claim 1  wherein the purified heat shock protein is a member of the hsp90 family.  
     
     
         5 . The method of  claim 3  wherein the purified heat shock protein is a member of the hsp90 family.  
     
     
         6 . The method of  claim 1 ,  2 ,  3 , or  4 , wherein the mammal is human.  
     
     
         7 . The method of  claim 4  or  5  wherein the heat shock protein is gp96.  
     
     
         8 . The method of  claim 4  or  5  wherein the heat shock protein is hsp90.  
     
     
         9 . The method of  claim 1  or  5  wherein the heat shock protein is hsp70.  
     
     
         10 . The method of  claim 7  wherein the amount of the heat shock protein present in the composition is in a range of 1 μg to 5000 μg.  
     
     
         11 . The method of  claim 7  wherein the amount of the heat shock protein present in the composition is in a range of 5 μg to 1500 μg.  
     
     
         12 . The method of  claim 7  wherein the amount of the heat shock protein present in the composition is in a range of 30 μg to 500 μg.  
     
     
         13 . The method of  claim 7  wherein the amount of the heat shock protein present in the composition is in a range of 50 μg to 200 μg.  
     
     
         14 . The method of  claim 13  wherein the composition is administered intradermally.  
     
     
         15 . The method of  claim 1  wherein the heat shock protein is a member of the hsp70 family.  
     
     
         16 . The method of  claim 3  wherein the heat shock protein is a member of the hsp70 family.  
     
     
         17 . The method of  claim 15  or  16  wherein the mammal is human.  
     
     
         18 . The method of  claim 1  or  3  wherein the heat shock protein is hsp70, hsp90, or gp96, or a combination of any of the foregoing.  
     
     
         19 . The method of  claim 18  wherein the mammal is human.  
     
     
         20 . The method of  claim 1  or  3  wherein the tissue is injured due to trauma.  
     
     
         21 . The method of  claim 20  wherein the trauma is due to burn, physical injury, or surgery.  
     
     
         22 . The method of  claim 1  or 3 wherein the tissue has an ischemic lesion, a malignant lesion, an infectious lesion, a degenerative lesion, a lesion associated with nutritional diseases or disorders, a lesion associated with a systemic disease, a lesion caused by a toxic substance, and a demyelinated lesion of the nervous system.  
     
     
         23 . The method according to  claim 1  or  3 , further comprising administering to the individual an effective amount of a biological response modifier selected from the group consisting of interferon-α, interferon-γ, interleukin-2, interleukin-4, interleukin-6, and tumor necrosis factor.  
     
     
         24 . The method according to  claim 1  or  3 , further comprising administering to the individual an effective amount of a wound healing factor.  
     
     
         25 . The method according to  claim 24  wherein the wound healing factor is selected from the group consisting of interferon (IFN)-β, IFN-γ, interleukin (IL)-1, IL-2, IL-4, IL-5, IL-15, tumor necrosis factor, flt-1 ligand, arginine, connective tissue growth factor, adenosine, cyclic adenosine monophosphate, the fibroblast growth factor family, tumor growth factor-α, tumor growth factor-β (1 and 2), vascular endothelial growth factor, the epidermal growth factor family, the platelet derived growth factor family, the insulin-like growth factor family, nitric oxide, macrophage-stimulating protein, and macrophage-derived growth factor.