Combined organ and hematopoietic cells for transplantation tolerance of grafts
View Patent ↗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 cryopreserved cellular product for establishing mixed chimerism in a solid organ transplant recipient, the product comprising:
greater than 5×10 5 CD34 + cells/kg recipient weight in a first cryopreservation solution comprising DMSO at a substantially neutral pH in a cryopreserved state; and
greater than 1×10 5 CD3 + cells/kg recipient weight in a second cryopreservation solution comprising DMSO at a substantially neutral pH in a cryopreserved state.
2. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are provided in separate containers.
3. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are provided as a mixture in a common container.
4. The cellular product of claim 1 , wherein at least one of the first cryopreservation solution and the second preservation solution comprises a polymeric carbohydrate.
5. The cellular product of claim 1 , wherein the first cryopreservation solution and the second preservation solution are different.
6. The cellular product of claim 1 , wherein the first cryopreservation solution and the second preservation solution are the same.
7. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA matched to an HLA type of the solid organ transplant recipient.
8. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to an HLA type of the solid organ transplant recipient.
9. The cellular product of claim 1 , wherein the CD34 + cells and the CD3 + cells are from a donor related to the solid organ transplant recipient.
10. The cellular product of claim 1 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
11. A cryopreserved cellular product for establishing mixed chimerism in a solid organ transplant recipient that is HLA matched to the solid organ transplant donor, the product comprising:
a cryopreservation solution comprising DMSO;
greater than 5×10 5 CD34 + cells/kg recipient weight in the cryopreservation solution, wherein the solid organ transplant donor's CD34 + cells are of an HLA type that is matched to the solid organ transplant recipient's HLA type; and
a defined amount of about 1×10 6 CD3 + cells/kg recipient weight in the cryopreservation solution, wherein the solid organ transplant donor's CD3 + cells are of an HLA type that is matched to the solid organ transplant recipient's HLA type,
wherein the cryopreserved product is in a cryopreserved state.
12. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are provided as a mixture in a common container comprising the cryopreservation solution.
13. The cellular product of claim 11 , wherein the cryopreservation solution comprises a polymeric carbohydrate.
14. The cellular product of claim 11 , wherein the cryopreservation solution comprises less than 10% DMSO.
15. The cellular product of claim 11 , wherein the product is at a substantially neutral pH.
16. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are HLA matched to the solid organ transplant recipient at all six alleles of HLA-A, HLA-B, and HLA-DR.
17. The cellular product of claim 11 , wherein the CD34 + cells and the CD3 + cells are from a donor related to the solid organ transplant recipient.
18. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
19. The cellular product of claim 11 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.
20. The cellular product of claim 11 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.
21. A cryopreserved 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 cryopreservation solution comprising DMSO in a cryopreserved state in a first vessel, 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 cryopreservation solution comprising DMSO in a cryopreserved state in a second vessel, 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.
22. The cellular product of claim 21 , wherein at least one of the first cryopreservation solution and the second preservation solution comprises a polymeric carbohydrate.
23. The cellular product of claim 21 , wherein the first cryopreservation solution and the second preservation solution are different.
24. The cellular product of claim 21 , wherein the first cryopreservation solution and the second preservation solution are the same.
25. The cellular product of claim 21 , wherein each of the first cryopreservation solution and the second cryopreservation solution comprises less than 10% DMSO.
26. The cellular product of claim 21 , wherein the CD34 + cells and the CD3 + cells are HLA mismatched to the solid organ transplant recipient at at least one of six alleles of HLA-A, HLA-B, and HLA-DR.
27. The cellular product of claim 11 , wherein the product is at a substantially neutral pH.
28. The cellular product of claim 21 , wherein CD34 + cells and the CD3 + cells are from a single apheresis product.
29. The cellular product of claim 21 , wherein CD34 + cells and the CD3 + cells are from multiple apheresis products.
30. The cellular product of claim 21 , wherein the solid organ is selected from the group consisting of heart, intestine, liver, lung, pancreas, and kidney.