Compositions, methods and uses of alpha 1-antitrypsin for early intervention in bone marrow transplantation and treatment of graft versus host disease

Abstract

Embodiments of the present invention relate to compositions and methods for treatment of subjects in need of or having a bone marrow transplant. Certain embodiments describe compositions and methods for treatment of conditions associated with bone marrow transplantations in a subject, for example, Graft versus Host Disease (GvHD) or bone marrow transplantation rejection. Some embodiments concern early or immediate bone marrow transplantation rejection. Certain embodiments relate to compositions and uses of alpha1-antitrypsin (α1-antitrypsin, AAT) and carboxyterminal peptide derivatives thereof and/or compositions and uses of serine protease inhibitors, immunomodulators or anti-inflammatory agent activity similar to that of AAT.

What is claimed: 
     
         1 . A method for treating or preventing acute graft versus host disease in a subject in need thereof, said method comprising administering to the subject a composition comprising alpha 1-antitrypsin (AAT) or mutant thereof or a carboxyterminal derivative thereof. 
     
     
         2 . The method of  claim 1 , wherein the composition is administered to the subject before transplantation, during transplantation, after transplantation or combination thereof 
     
     
         3 . The method of  claim 1 , wherein the composition further comprises one or more anti-transplant rejection agent, anti-inflammatory agent, immunosuppressive agent, immunomodulatory agent, anti-microbial agent, or a combination thereof. 
     
     
         4 . The method of  claim 1 , wherein administration occurs within 30 to 40 days after bone marrow transplantation. 
     
     
         5 . The method of  claim 1 , wherein administration occurs immediately after bone marrow transplantation. 
     
     
         6 . The method of  claim 1 , further comprising treating the subject soon after transplantation and preventing mortality of the subject compared to a subject not treated with the composition. 
     
     
         7 . A method for reducing or preventing bone marrow transplant rejection in a subject having or in need of a bone marrow transplant, said method comprising:
 administering bone marrow cells to the subject;   administering one or more dose of a composition comprising AAT, mutant thereof or carboxyterminal derivative thereof to the subject within two weeks of transplantation of the bone marrow cells; and   preventing GvHD in the subject.   
     
     
         8 . The method of  claim 7 , wherein the composition is AAT. 
     
     
         9 . The method of  claim 7 , wherein the composition further comprises anti-inflammatory agents. 
     
     
         10 . The method of  claim 7 , wherein the composition further comprises one or more anti-inflammatory agent, immunosuppressive agent, immunomodulatory agent, anti-microbial agent, or a combination thereof. 
     
     
         11 . The method of  claim 7 , wherein the composition reduces the production of one or more cytokines. 
     
     
         12 . The method of  claim 7 , wherein the composition further comprises antibodies to proinflammatory cytokines. 
     
     
         13 . A method for preserving ex vivo bone marrow cells for transplantation, said method comprising exposing the bone marrow cells to a composition comprising AAT, a mutant thereof or carboxyterminal derivative thereof. 
     
     
         14 . The method of  claim 13 , wherein preserving the bone marrow cells comprises preserving the bone marrow cells prior to implanting the bone marrow cells into a recipient. 
     
     
         15 . The method of  claim 13 , wherein preserving the bone marrow cells is selected from the group consisting of reducing apoptosis, reducing cytokine production, reducing nitric oxide production and a combination thereof. 
     
     
         16 . A method for reducing need of immunosuppressive agents in a subject having a bone marrow transplantation comprising; identifying a subject having a bone marrow cell transplant and administering a therapeutically effective amount of AAT, AAT mutant or carboxyterminal derivative of AAT to the subject and reducing the need for immunosuppressive therapy in the subject. 
     
     
         17 . The method of  claim 16 , wherein the subject is administered the composition before and immediately after bone marrow transplantation. 
     
     
         18 . The method of  claim 16 , wherein the subject is suffering from a condition selected from leukemia, severe aplastic anemia, lymphoma, multiple myeloma, immune deficiency disorder, solid-tumor cancer, breast cancer, ovarian cancer and other conditions.