Natural killer cells from placenta

Patent metadata

Field	Value
Publication number	US-9763983-B2
Application number	US-201414764873-A
Country	US
Kind code	B2
Filing date	Feb 4, 2014
Priority date	Feb 5, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

Provided herein are placental perfusate, placental perfusate cells, placenta-derived intermediate natural killer cells, combined natural killer cells from placenta and umbilical cord blood, and combinations thereof. Also provided herein are compositions comprising the same, and methods of using placental perfusate, placental perfusate cells, placenta-derived intermediate natural killer cells, and combined natural killer cells and combinations thereof, to suppress the growth or proliferation of tumor cells, cancer cells, and the like, and to treat individuals having tumor cells. Also provided herein are methods of treating an individual having a tumor or graft-versus-host disease with placental perfusate, placental perfusate-derived cells, natural killer cells from placenta, e.g., from placental perfusate, and/or combined natural killer cells comprising natural killer cells from placenta, e.g., from placental perfusate, and umbilical cord blood.

First claim

What is claimed is:

1. A method of treating or preventing graft-versus-host disease, comprising administering natural killer cells isolated from human placental perfusate and umbilical cord blood to a patient with or at risk of developing graft-versus-host disease, wherein said patient has received a solid organ transplant or a composite tissue allograft.

2. The method of claim 1 , wherein said human placental perfusate and umbilical cord blood has been treated to remove a plurality of erythrocytes.

3. The method of claim 1 , wherein said natural killer cells comprise at least about 50% CD56 + cells.

4. The method of claim 1 , wherein said natural killer cells comprise at least about 50% CD56 + CD16 − cells.

5. The method of claim 1 , wherein said natural killer cells are contacted with an immunomodulatory compound in an amount and for a time sufficient for said cells to express detectably more granzyme B than an equivalent number of cells not contacted with said immunomodulatory compound.

6. The method of claim 5 , wherein said immunomodulatory compound is lenalidomide or pomalidomide.

7. The method of claim 1 , wherein said natural killer cells comprise:
a detectably higher number of CD3 − CD56 + CD16 − natural killer cells than an equivalent number of natural killer cells from peripheral blood;
a detectably lower number of CD3 − CD56 + CD16 + natural killer cells than an equivalent number of natural killer cells from peripheral blood;
a detectably higher number of CD3 − CD56 + KIR2DL2/L3 + natural killer cells than an equivalent number of natural killer cells from peripheral blood;
a detectably lower number of CD3 − CD56 + NKp46 + natural killer cells than an equivalent number of natural killer cells from peripheral blood;
a detectably higher number of CD3 − CD56 + NKp30 + natural killer cells than an equivalent number of natural killer cells from peripheral blood;
a detectably higher number of CD3 − CD56 + 2B4 + natural killer cells than an equivalent number of natural killer cells from peripheral blood; or
a detectably higher number of CD3 − CD56 + CD94 + natural killer cells than an equivalent number of natural killer cells from peripheral blood.

8. The method of claim 1 , wherein said natural killer cells have not been cultured.

9. The method of claim 1 , wherein said natural killer cells have been cultured.

10. The method of claim 9 , wherein said natural killer cells have been cultured for about 21 days.

11. The method of claim 9 , wherein said natural killer cells have been cultured in the presence of feeder cells.

12. The method of claim 11 , wherein additional feeder cells are added to the culture at about day 7.

13. The method of claim 1 , wherein said patient has received a solid organ transplant.

14. The method of claim 1 , wherein said patient has received a composite tissue allograft.

15. The method of claim 1 , wherein said graft-versus-host disease is reduced in grade by at least one step by said administering.

16. The method of claim 1 , wherein said graft-versus-host disease does not progress beyond grade II within 100 days after transplantation as a result of said administering.

17. The method of claim 1 , wherein said graft-versus-host disease does not progress beyond grade I within 100 days after transplantation as a result of said administering.

18. The method of claim 1 , wherein said natural killer cells express one or both of miRNAs hsa-miR-422a and hsa-miR-549.

19. The method of claim 1 , wherein the natural killer cells express one or more of miRNAs hsa-miR-125b, hsa-miR-198, hsa-miR-450, hsa-miR-519c, hsa-miR-520c, hsa-miR-522, hsa-miR-524, and hsa-miR-627 at a detectably greater amount than an equivalent number of natural killer cells from peripheral blood.

20. The method of claim 9 , wherein the natural killer cells express one or more of miRNAs hsa-miR-450, hsa-miR-520c, hsa-miR-524, and hsa-miR-627 at a detectably greater amount than an equivalent number of natural killer cells from peripheral blood.

Assignees

• Anthrogenesis Corp

Inventors

• Zhang Xiaokui
• Hariri Robert J
• Voskinarian-Berse Vanessa
• Kang Lin
• Law Eric
• Abbot Stewart

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/06

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

• A61P35/02

  specific for leukemia · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61K2035/122

  for inducing tolerance or supression of immune responses · CPC title