Compositions and methods related to graft versus host disease and treatments thereof

Abstract

Embodiments of the present invention illustrate methods of treating and preventing transplantation and side effects associated with transplantation. In particular, the present invention relates to compositions and methods for inhibition of graft rejection and promotion of graft survival. Thus, the invention relates to modulation of cellular activities, including graft rejection, promotion of graft survival, graft versus host rejection and conditions commonly associated with graft rejection. More particularly, the present invention relates to the inhibitory compounds comprising naturally occurring and man-made inhibitors of serine protease and inducers of other alpha1-antitrypsin activities.

What is claimed: 
     
         1 . A method for reducing risk of graft versus host disease (GVHD) in a subject, administering to the subject at risk of developing GVHD, a composition comprising alpha-1 antitrypsin (AAT) or cleavage product thereof, or recombinant molecule thereof, or ketone or aldehyde derivative thereof, and a pharmaceutically acceptable excipient, and reducing the risk of developing GVHD or reducing effects of GVHD in the subject. 
     
     
         2 . The method of  claim 1 , wherein administering comprises administering an AAT recombinant molecule comprising a fusion of full-length AAT polypeptide or cleavage product thereof, fused to an immunoglobulin molecule or to a domain of an immunoglobulin molecule or to GST. 
     
     
         3 . The method of  claim 1 , further comprising administering one or more anti-rejection agent, anti-inflammatory agent, immunosuppressive agent, immunomodulatory agent, anti-microbial agent, anti-viral or combination thereof to the subject. 
     
     
         4 . The method of  claim 1 , wherein the GVHD is attributed to a stem cell or bone marrow implant in the subject. 
     
     
         5 . The method of  claim 4 , wherein the GVHD is attributed to bone marrow implantation and the subject is administered the composition following the bone marrow implantation. 
     
     
         6 . The method of  claim 2 , wherein the immunoglobulin domain comprises an IgG1 constant region. 
     
     
         7 . The method of  claim 1 , wherein the composition is a dose of about 0.1 mg/kg to about 100 mg/kg. 
     
     
         8 . A method for treating a subject having graft versus host disease (GVHD), said method comprising administering to the subject a composition comprising alpha-1antitrypsin (AAT) or recombinant thereof, and a pharmaceutically acceptable excipient, wherein administering AAT or recombinant thereof to the subject treats the subject. 
     
     
         9 . The method of  claim 8 , wherein the recombinant AAT is an AAT fusion polypeptide comprising full-length alph-1 antitrypsin or a cleavage product thereof, fused to an immunoglobulin molecule or to a domain of an immunoglobulin molecule or to GST. 
     
     
         10 . A method for reducing risk of graft versus host disease (GVHD) in a subject comprising, administering to the subject at risk of developing GVHD, a composition consisting essentially of alpha-1 antitrypsin (AAT) or cleavage product thereof, or recombinant molecule thereof, or ketone or aldehyde derivative thereof, and a pharmaceutically acceptable excipient, to reduce the risk of developing GVHD or reduce effects of GVHD in the subject. 
     
     
         11 . The method of  claim 10 , wherein the composition is administered after organ or non-organ transplantation to reduce incidence of GVHD or effects of GVHD in the subject as compared to a control subject not receiving the composition. 
     
     
         12 . The method of  claim 10 , wherein the recombinant AAT is an AAT fusion polypeptide comprising full-length alpha1-antitrypsin or a cleavage product thereof, fused to an immunoglobulin molecule or to a domain of an immunoglobulin molecule or to GST. 
     
     
         13 . A composition comprising a combination of alpha-1 antitrypsin (AAT) and an antimicrobial agent, for use in a method to treat steroid-refractory GVHD.