Compositions for establishing mixed chimerism and methods of manufacture thereof

Abstract

The invention provides compositions for establishing mixed chimerism in a subject. The compositions include CD34 + cells that have been column-purified from an apheresis product and CD3 + cells from an apheresis product that have not been purified through a column. The invention also provides methods of making and using such compositions.

What is claimed is: 
     
         1 . A cellular product for establishing mixed chimerism in a solid organ transplant recipient, the product comprising:
 column purified CD34 +  cells derived from an apheresis product; and   CD3 +  cells derived from the apheresis product that have not passed through a purification column.   
     
     
         2 . The cellular product of  claim 1 , comprising at least about 5×10 5  CD34 +  cells/kg recipient weight. 
     
     
         3 . The cellular product of  claim 1 , comprising at least about 5×10 5  CD3 +  cells/kg recipient weight. 
     
     
         4 . The cellular product of  claim 1 , comprising at least about 5×10 5  CD34 +  cells/kg recipient weight and about 5×10 5  CD3 +  cells/kg recipient weight. 
     
     
         5 . The cellular product of  claim 1 , comprising at least about 5×10 7  CD3 +  solid organ transplant donor derived cells/kg recipient weight. 
     
     
         6 . The cellular product of  claim 1 , comprising at least about 5×10 5  CD34 +  solid organ transplant donor derived cells/kg recipient weight and at least about 5×10 7  CD3 +  solid organ transplant donor derived cells/kg recipient weight. 
     
     
         7 . The cellular product of  claim 1 , wherein the CD34 +  cells and the CD3 +  cells are provided in separate containers. 
     
     
         8 . The cellular product of  claim 1 , wherein the CD34 +  cells and the CD3 +  cells are provided as a mixture in a common container. 
     
     
         9 . The cellular product of  claim 1 , wherein the apheresis product is from a solid organ transplant donor of an HLA type that is matched to the recipient's HLA type. 
     
     
         10 . The cellular product of  claim 1 , wherein the apheresis product is from a solid organ transplant donor of an HLA type that is mismatched to the recipient's HLA type. 
     
     
         11 . A cellular product for establishing mixed chimerism in a solid organ transplant recipient, the product comprising:
 column purified CD34 +  cells derived from an apheresis product in an amount greater than 5×10 5  CD34 +  cells/kg recipient weight; and   CD3 +  cells derived from the apheresis product that have not passed through a purification column in an amount greater than 1×10 5  CD3 +  cells/kg recipient weight.   
     
     
         12 . The cellular product of  claim 11 , comprising at least about 4×10 6  CD34 +  cells/kg recipient weight. 
     
     
         13 . The cellular product of  claim 11 , comprising at least about 5×10 5  CD3 +  cells/kg recipient weight. 
     
     
         14 . The cellular product of  claim 11 , comprising at least about 4×10 6  CD34 +  cells/kg recipient weight and about 5×10 5  CD3 +  cells/kg recipient weight. 
     
     
         15 . The cellular product of  claim 11 , comprising at least about 5×10 7  CD3 +  solid organ transplant donor derived cells/kg recipient weight. 
     
     
         16 . The cellular product of  claim 11 , comprising at least about 4×10 6  CD34 +  solid organ transplant donor derived cells/kg recipient weight and at least about 5×10 7  CD3 +  solid organ transplant donor derived cells/kg recipient weight. 
     
     
         17 . The cellular product of  claim 1 , wherein the CD34 +  cells and the CD3 +  cells are provided in separate containers. 
     
     
         18 . The cellular product of  claim 11 , wherein the CD34 +  cells and the CD3 +  cells are provided as a mixture in a common container. 
     
     
         19 . The cellular product of  claim 1 , wherein the apheresis product is from a solid organ transplant donor of an HLA type that is matched to the recipient's HLA type. 
     
     
         20 . The cellular product of  claim 11 , wherein the apheresis product is from a solid organ transplant donor of an HLA type that is mismatched to the recipient's HLA type. 
     
     
         21 . A cellular product for establishing mixed chimerism in a solid organ transplant recipient, the cellular product comprising component A and component B;
 wherein component A comprises CD34 +  cells that have been purified from a first portion of a non-column purified apheresis product in an amount greater than 5×10 5  CD34 +  cells/kg recipient weight; and   wherein component B comprises a second portion of the non-column purified apheresis product comprising CD3 +  cells in an amount greater than 1×10 5  CD3 +  cells/kg recipient weight.   
     
     
         22 . The cellular product of  claim 21 , wherein component A comprises at least about 4×10 6  CD34 +  cells/kg recipient weight. 
     
     
         23 . The cellular product of  claim 21 , wherein component B comprises at least about 5×10 5  CD3 +  cells/kg recipient weight. 
     
     
         24 . The cellular product of  claim 21 , wherein component A comprises at least about 4×10 6  CD34 +  cells/kg recipient weight and component B comprises about 5×10 5  CD3 +  cells/kg recipient weight. 
     
     
         25 . The cellular product of  claim 21 , wherein component B comprises at least about 5×10 7  CD3 +  solid organ transplant donor derived cells/kg recipient weight. 
     
     
         26 . The cellular product of  claim 21 , wherein component A comprises at least about 4×10 6  CD34 +  solid organ transplant donor derived cells/kg recipient weight and component B comprises at least about 5×10 7  CD3 +  solid organ transplant donor derived cells/kg recipient weight. 
     
     
         27 . The cellular product of  claim 21 , wherein component A and component B are provided in separate containers. 
     
     
         28 . The cellular product of  claim 21 , wherein component A and component B are provided as a mixture in a common container. 
     
     
         29 . The cellular product of  claim 21 , wherein the apheresis product is from a solid organ transplant donor of an HLA type that is matched to the recipient's HLA type. 
     
     
         30 . The cellular product of  claim 21 , wherein the apheresis product is from a solid organ transplant donor of an HLA type that is mismatched to the recipient's HLA type.