Natural killer cells from placenta

• US 9,763,983 B2
• Filed: 02/04/2014
• Issued: 09/19/2017
• Est. Priority Date: 02/05/2013
• Status: Active Grant

• Current Assignee: Celularity, Inc.
• Original Assignee: Anthrogenesis Corporation (Bristol-Myers Squibb Company)
• Inventors: Zhang, Xiaokui, Hariri, Robert J., Voskinarian-Berse, Vanessa, Kang, Lin, Law, Eric, Abbot, Stewart
• Primary Examiner(s): Gangle, Brian J
• Application Number:
  US14/764,873
• Publication Number:
  US 20150366910A1
• Time in Patent Office: 1,323 Days
• Field of Search: None
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 39/4613 Natural-killer cells [NK or NK-T]
• CPC Class Codes: A61K 39/4621 immunosuppressive or immunotolerising
• CPC Class Codes: A61K 39/46434 Antigens related to induction of tolerance to non-self
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C12N 2501/05 Adjuvants
• CPC Class Codes: C12N 5/0646 Natural killers cells [NK], NKT cells

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.

Claims

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.