Combined organ and hematopoietic cells for transplantation tolerance of HLA mismatched grafts
Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to an HLA mismatched 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 method for establishing mixed chimerism in a solid organ transplant recipient comprising:
infusing a recipient of a transplantation of a solid organ from a donor with an engineered hematopoietic cell composition, wherein the recipient is HLA mismatched from the donor, said engineered hematopoietic cell composition comprising:
an effective amount of CD34 + cells/kilogram recipient weight and more than 1×10 7 CD3 + T cells/kilogram recipient weight, wherein the donor's CD34 + cells and CD3 + cells are of an HLA type that is mismatched to the solid organ transplant recipient's HLA type.
2. The method of claim 1 , wherein said effective amount of purified CD34 + cells/kilogram recipient weight comprises at least 1×10 7 purified CD34 + cells/kilogram recipient weight.
3. The method of claim 1 , wherein said effective amount of CD3 + T cells/kilogram recipient weight comprises at least 4×10 7 CD3 + T cells/kilogram recipient weight.
4. The method of claim 1 , wherein said effective amount of CD3 + T cells/kilogram recipient weight comprises about 5×10 7 CD3 + T cells/kilogram recipient weight.
5. The method of claim 1 , wherein a donor of said solid organ and a donor of said engineered hematopoietic cell composition are the same.
6. The method of claim 1 , wherein a donor of said solid organ is a human.
7. The method of claim 1 , wherein a donor of said engineered hematopoietic cell composition is a human.
8. The method of claim 1 , wherein said solid organ is selected from a group consisting of a kidney, a heart, an intestine, a liver, a lung, and a pancreas.
9. The method of claim 1 , wherein said engineered hematopoietic cell composition is isolated and purified from a deceased or living donor.
10. The method 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.
11. The method 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.
12. The method of claim 1 , wherein the CD34 + cells and the CD3 + cells are from a single apheresis product.
13. The method of claim 1 , wherein the engineered hematopoietic cell composition was cryopreserved in a cryopreservation solution prior to the infusing.
14. The method of claim 13 , wherein the cryopreservation solution comprises DMSO.
15. The method of claim 14 , wherein engineered hematopoietic cell composition further comprises an isotonic excipient.