Human facilitating cells
View Patent ↗The present disclosure relates to human facilitating cells (hFC), and methods of isolating, characterizing, and using such hFCs.
1. A therapeutic cellular composition for delivery to a recipient, the composition comprising:
human hematopoietic stem cells (HSCs) from a donor, wherein the HSCs have a phenotype of CD34+;
human facilitating cells (hFCs) from the donor, wherein the hFCs comprise cells having a phenotype of CD8+/alpha beta TCR−/CD56 dim/neg and cells having a phenotype of CD8+/alpha beta TCR−/CD56 bright ; and
human alpha beta TCR+ T cells from the donor, wherein the alpha beta TCR+ T cells are present in the composition in a therapeutic amount that is between about 2.0×10 6 and 5.0×10 6 alpha beta TCR+ T cells per kilogram of the recipient's body weight.
2. The therapeutic cellular composition of claim 1 , wherein the alpha beta TCR+ T cells are present in the composition in a therapeutic amount between about 3.0×10 6 and about 4.2×10 6 alpha beta TCR+ T cells per kilogram of the recipient's body weight.
3. The therapeutic cellular composition of claim 1 , wherein the alpha beta TCR+ T cells are present in the composition in a therapeutic amount of about 3.2×10 6 alpha beta TCR+ T cells per kilogram of the recipient's body weight.
4. The therapeutic cellular composition of claim 1 , wherein the alpha beta TCR+ T cells are present in the composition in a therapeutic amount of about 3.8×10 6 alpha beta TCR+ T cells per kilogram of the recipient's body weight.
5. The therapeutic composition of claim 1 , wherein the donor and the recipient are syngeneic to one another.
6. The cellular composition of claim 1 , wherein the hFCs having a phenotype of CD8+/alpha beta TCR−/CD56 dim/neg are predominantly CD3 epsilon+/CD19−.
7. The cellular composition of claim 1 , wherein the hFCs having a phenotype of CD8+/alpha beta TCR−/CD56 bright are predominantly CD3 epsilon−/CD19+.
8. The cellular composition of claim 1 , wherein the hFCs comprise cells having a phenotype of CD8+/alpha beta TCR−/delta gamma TCR+/CD3 epsilon+/CD19+.
9. The cellular composition of claim 1 , wherein the hFCs comprise cells having a phenotype of CD8+/alpha beta TCR−/B220+/CD11c+/CD11b−.
10. A method of making the immune system of a recipient chimeric with the immune system of a donor, comprising:
administering the therapeutic cellular composition of claim 1 to the recipient.
11. The method of claim 10 , wherein the recipient has been conditioned.
12. The method of claim 11 , wherein the conditioning of the recipient includes a dose of total body irradiation (TBI) that does not exceed 300 cGy.
13. The method of claim 10 , wherein the therapeutic cellular composition is administered to the recipient intravenously.
14. The method of claim 10 , wherein the recipient's immune system is considered to be chimeric with the donor's immune system when the recipient's immune system is at least about 1% donor origin for greater than 6 month.
15. The method of claim 10 , wherein the recipient has a disease.
16. The method of claim 15 , wherein the disease is selected from the group consisting of an autoimmune disease, leukemia, an inherited metabolic disorder, infection by an immunodeficiency virus, infection by a hepatitis virus, a hematopoietic malignancy, anemia, hemoglobinopathies, an enzyme deficiency, and a disease that necessitates an organ transplant.
17. The method of claim 16 , wherein the autoimmune disease is selected from the group consisting of diabetes, multiple sclerosis, and systemic lupus erythematosus.
18. The method of claim 16 , wherein the organ is selected from the group consisting of heart, skin, liver, lung, kidney, pancreas, thyroid gland, parathyroid gland, thymus, adrenal cortex, and adrenal medulla.