Combined organ and hematopoietic cells for transplantation tolerance of grafts
Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.
1. A cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA mismatched from the solid organ transplant donor, the product comprising:
greater than 5×10 5 CD34 + solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD34 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type; and
greater than 4×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight, wherein the solid organ transplant donor's CD3 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type.
2. The cellular product of claim 1 , comprising at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight.
3. The cellular product of claim 1 , comprising at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.
4. The cellular product of claim 1 , 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.
5. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at least one of six alleles of HLA-A, HLA-B, and HLA-DR.
6. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at all six HLA alleles.
7. The cellular product of claim 1 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
8. The cellular product of claim 1 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.
9. The cellular product of claim 1 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.
10. The cellular product of claim 9 , wherein the solid organ is a kidney.
11. A cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA mismatched from the solid organ transplant donor, the product comprising:
greater than 5×10 5 CD34 + solid organ transplant donor derived cells/kg recipient weight in a first container, wherein the solid organ transplant donor's CD34 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type; and
greater than 4×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight in a second container, wherein the solid organ transplant donor's CD3 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type.
12. The cellular product of claim 11 , comprising at least about 4×10 6 CD34 + solid organ transplant donor derived cells/kg recipient weight.
13. The cellular product of claim 11 , comprising at least about 5×10 7 CD3 + solid organ transplant donor derived cells/kg recipient weight.
14. 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.
15. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at least one of six alleles of HLA-A, HLA-B, and HLA-DR.
16. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at all six HLA alleles.
17. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
18. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.
19. The cellular product of claim 11 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.
20. The cellular product of claim 19 , wherein the solid organ is a kidney.