Universal donor-derived tolerogenic cells for inducing non-syngeneic transplantation tolerance

Abstract

The present invention provides a method of treating a disease in a subject in need thereof via non-syngeneic graft administration without or with reduced concomitant graft rejection. The method comprises administering to the subject a therapeutically effective graft being non-syngeneic with the subject, and a dose of tolerogenic cells being non-syngeneic with both the subject and the graft for preventing or reducing graft rejection in the subject, thereby treating the disease in the subject

What is claimed is: 
     
         1 . A method of treating a disease in a subject in need thereof via non-syngeneic graft administration without or with reduced concomitant graft rejection, the method comprising:
 (a) administering to the subject a therapeutically effective graft being non-syngeneic with the subject, said graft being selected from the group consisting of a cardiac graft, a cardiovascular graft, a cartilage graft, a connective tissue graft, a dermal graft, a gastrointestinal graft, a glandular graft, a hepatic graft, a hematopoietic cell graft, a muscle graft, a neurological graft, an ocular graft, an osseous graft, a pancreatic graft, a pulmonary graft, a renal graft and a stem cell graft, and   (b) administering to the subject a dose of primary tolerogenic cells for reducing in a subject rejection of said graft, said tolerogenic cells being CD4+CD25+ cells and wherein said tolerogenic cells are allogeneic and MHC-mismatched with the subject and with said graft, and wherein said primary tolerogenic cells are from one donor, thereby treating the disease in the subject.   
     
     
         2 . The method of  claim 1 , further comprising administering at least one immunosuppressant drug to the subject. 
     
     
         3 . The method of  claim 1 , wherein said dose of said tolerogenic cells is selected from a range of about 1 million cells per kilogram body weight to about 400 million cells per kilogram body weight. 
     
     
         4 . The method of  claim 1 , wherein said administering of said tolerogenic cells is effected prior to and/or concomitantly with said administering of said graft. 
     
     
         5 . The method of  claim 1 , further comprising the step of conditioning the subject under sublethal, lethal or supralethal conditions prior to said administering of said graft to the subject and/or prior to said administering of said dose of tolerogenic cells to the subject. 
     
     
         6 . The method of  claim 1 , wherein said graft is allogeneic with the subject. 
     
     
         7 . The method of  claim 1 , wherein said graft is allogeneic and MHC-mismatched with the subject. 
     
     
         8 . A method of preventing or reducing in a subject rejection of a graft being non-syngeneic with the subject, the method comprising:
 (a) administering the graft to the subject, said graft being selected from the group consisting of a cardiac graft, a cardiovascular graft, a cartilage graft, a connective tissue graft, a dermal graft, a gastrointestinal graft, a glandular graft, a hepatic graft, a hematopoietic cell graft, a muscle graft, a neurological graft, an ocular graft, an osseous graft, a pancreatic graft, a pulmonary graft, a renal graft and a stem cell graft; and   (b) administering to the subject a dose of primary tolerogenic cells, said tolerogenic cells being CD4+CD25+ cells and wherein said tolerogenic cells are allogeneic and MHC-mismatched with the subject and with the graft, and wherein said primary tolerogenic cells are from one cell donor, thereby preventing or reducing in the subject rejection of the graft.   
     
     
         9 . The method of  claim 8 , further comprising administering at least one immunosuppressant drug to the subject. 
     
     
         10 . The method of  claim 8 , wherein said dose of said tolerogenic cells is selected from a range of about 1 million cells per kilogram body weight to about 400 million cells per kilogram body weight. 
     
     
         11 . The method of  claim 8 , wherein said administering of said tolerogenic cells is effected prior to and/or concomitantly with said administering of the graft. 
     
     
         12 . The method of  claim 8 , further comprising the step of conditioning the subject under sublethal, lethal or supralethal conditions prior to said administering of the graft to the subject and/or prior to said administering of said dose of tolerogenic cells to the subject. 
     
     
         13 . The method of  claim 8 , wherein the graft is allogeneic with the subject. 
     
     
         14 . The method of  claim 8 , wherein the graft is allogeneic and MHC-mismatched with the subject.