Human facilitating cells

Patent metadata

Field	Value
Publication number	US-9452184-B2
Application number	US-201414157888-A
Country	US
Kind code	B2
Filing date	Jan 17, 2014
Priority date	May 30, 2008
Publication date	Sep 27, 2016
Grant date	Sep 27, 2016

Abstract

The present disclosure relates to human facilitating cells (hFC), and methods of isolating, characterizing, and using such hFCs.

First claim

What is claimed is:

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.

Assignees

• Univ Louisville Res Found Inc

Inventors

• Ildstad Suzanne T
• Elliott Mary Jane

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/02

  Immunomodulators · CPC title