Compositions for establishing mixed chimerism and methods of manufacture thereof
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.
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
a non-column purified portion of the apheresis product that comprises CD3 + cells in an amount greater than 1×10 5 CD3 + cells/kg recipient weight and circulating factors from blood of a donor of the apheresis product.
2. The cellular product of claim 1 , wherein the non-column purified portion of the apheresis product comprises non-column purified CD34 + cells and the CD3 + cells, and further wherein the column purified CD34 + cells derived from the apheresis product and the non-column purified CD34 + cells together provide the cellular product with at least about 5×10 5 CD34 + cells/kg recipient weight.
3. The cellular product of claim 1 , wherein the non-column purified portion of the apheresis product comprises 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 Human Leukocyte Antigen (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
a non-column purified portion of the apheresis product that comprises CD3 + cells in an amount greater than 1×10 5 CD3 + cells/kg recipient weight and circulating factors from blood of a donor of the apheresis product.
12. The cellular product of claim 11 , wherein the non-column purified portion of the apheresis product further comprises non-column purified CD34 + cells and wherein the cellular product comprises 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 11 , 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 11 , 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 circulating factors from blood of a donor of the apheresis product, and non-column purified CD34 + cells.
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.