IP Library Granted Patent US 10,813,949
Granted Patent B2
US 10,813,949 · App. 15/781,447 · Granted Oct 27, 2020

Uses of expanded populations of hematopoietic stem/progenitor cells

Inventor: Colleen Delaney (Seattle, WA)
Assignee: FRED HUTCHINSON CANCER RESEARCH CENTER
A61K35/14A61K35/28A61K35/51A61K39/001A61K2035/122
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Quick Facts
Patent No.
US 10,813,949
App. No.
15/781,447
Granted
Oct 27, 2020
Kind
B2
Abstract

Uses of expanded cord blood hematopoietic stem/progenitor cells (HSPC) are described. Examples include to reduce transplant rejection, to induce immune tolerance, to reduce total parenteral nutrition (TPN) feeding, opioid use, mucositis, and hospitalization following a medical procedure and to reduce graft versus host disease (GVHD) following an allogeneic transplant.

Claims (32)

1. A method of inducing immune tolerance in a transplant recipient comprising:

administering a therapeutically effective amount of a CD34+ enriched and expanded cord blood product that does not include mature T cells to the transplant recipient, thereby inducing immune tolerance in the transplant recipient wherein the cord blood product is HLA-unmatched to the transplant recipient and the transplant is allogeneic.

2. The method of claim 1 , wherein the cord blood product was expanded in a culture comprising a Notch agonist.

3. The method of claim 1 , wherein the cord blood product was previously cryo-preserved.

4. The method of claim 1 , wherein the cord blood product was derived from the umbilical cord blood and/or placental blood of a single human at birth.

5. The method of claim 1 , wherein the cord blood product comprises a pool of two or more different expanded human cord blood stem cell populations, each different population in the pool derived from the umbilical cord blood and/or placental blood of a different human at birth and wherein blood stem cell populations are pooled without immunological matching to each other or to the transplant recipient.

6. The method of claim 1 , wherein immune tolerance in the transplant recipient is evidenced by improved transplant outcomes related to immune responsiveness, the outcomes selected from (a) by reduced transplant rejection as compared to a reference population not receiving the cord blood product, or (b) reduced administration of immuno-suppressant drugs as compared to a reference population not receiving the cord blood product.

7. The method of claim 1 , wherein the administering of the cord blood product to the transplant recipient occurs before receipt of the transplant.

8. The method of claim 1 , wherein the administering of the cord blood product to the transplant recipient is within 36 hours of receiving the transplant.

9. The method of claim 8 , wherein the administering of the cord blood product to the transplant recipient is within 12 hours of receiving the transplant.

10. The method of claim 1 , wherein the transplant recipient is a pediatric transplant recipient.

11. The method of claim 1 , wherein the transplant is a solid tissue transplant.

12. A method to improve transplant outcome in a recipient of a transplant, comprising administering to a recipient of a transplant a therapeutically effective amount of a Notch agonist expanded cord blood product which does not include mature T cells, wherein the expanded cord blood product is HLA-unmatched to the recipient, in which improved transplant outcome is evidenced by one or more of:

(a) reduced total parenteral nutrition (TPN) in the recipient;

(b) reduced amount or frequency of opioid treatments in the recipient;

(c) reduced hospitalization time of the recipient;

(d) reduced mucositis in the recipient; and

(e) reduced Stage III and Stage IV acute graft versus host disease in the recipient, as compared to a reference population of transplant recipients not receiving the expanded cord blood product.

13. The method of claim 12 , wherein the cord blood product was previously cryo-preserved.

14. The method of claim 12 , wherein the cord blood product is derived from the umbilical cord blood and/or placental blood of a single human at birth.

15. The method of claim 12 , wherein the cord blood product comprises a pool of two or more different expanded human cord blood stem cell populations, each different population in the pool derived from the umbilical cord blood and/or placental blood of a different human at birth and wherein blood stem cell populations are pooled without immunological matching to each other or to the transplant recipient.

16. The method of claim 12 , wherein the administering of the cord blood product to the transplant recipient occurs before receipt of the transplant.

17. The method of claim 12 , wherein the administering of the cord blood product to the transplant recipient is within 36 hours of receiving the transplant.

18. The method of claim 17 , wherein the administering of the cord blood product to the transplant recipient is within 12 hours of receiving the transplant.

19. The method of claim 12 , wherein the transplant is allogeneic.

20. The method of claim 12 , wherein the transplant recipient is a pediatric transplant recipient.

21. The method of claim 12 , wherein the transplant is a solid tissue transplant.

22. The method of claim 21 , wherein the transplant comprises adipose tissue, a blood vessel, bone, bone marrow, cardiac cells, cartilage, cartilaginous cells, chondral cells, cochlea, connective tissue, a cornea, cultured cell monolayers, dental tissue, an eye, a face, fascia, fibrous tissue, a foot, a functional spine unit, hair, a hand, a heart, a heart valve, intestine, islet cells, kidney, a lens, a ligament, liver, lung, meniscus, muscle-tendon grafts, muscle tissue, neural cells, neural tissue, osteochondral cells, osteogenic cells, an ovary, pancreas, semi-tendinous tissues, skin, spleen, stomach, tendons, testis, a tooth, or a vertebral disc.

23. A method for reducing acute graft versus host disease (GvHD) in an allogeneic transplant recipient at risk of GvHD, comprising administering to the transplant recipient a therapeutically effective amount of an unmatched CD34+ enriched and expanded cord blood product that does not contain mature T cells, thereby reducing acute GvHD in the transplant recipient.

24. A method for reducing rejection of allogeneic tissue in a transplant recipient, comprising administering to the transplant recipient a therapeutically effective amount of an unmatched CD34+ enriched and expanded cord blood product that does not contain mature T cells, thereby reducing rejection of the allogeneic tissue.

25. The method of claim 24 , wherein the tissue is a skin graft.

26. The method of claim 24 , wherein the tissue comprises solid tissue.

Assignments (3)
CONFIRMATORY LICENSE Recorded Mar 27, 2019
From: FRED HUTCHINSON CANCER RESEARCH CENTER
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 048721/0174 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 19, 2018
From: DELANEY, COLLEEN
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 046915/0817 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 19, 2018
From: DELANEY, COLLEEN
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 046915/0839 →
Continuity (3)
Provisional Application 62263470 · Dec 4, 2015
Provisional Application 62263573 · Dec 4, 2015
Related Publication 20180353541A1 · Dec 13, 2018