Reducing immunogenicity of xenogeneic transplant tissues

Patent metadata

Field	Value
Publication number	US-9883939-B2
Application number	US-201314399119-A
Country	US
Kind code	B2
Filing date	May 8, 2013
Priority date	May 8, 2012
Publication date	Feb 6, 2018
Grant date	Feb 6, 2018

Abstract

Methods of preparing and porcine cells, organs and tissues that have reduced immunogenicity, e.g., for transplant into humans, e.g., for the treatment of burn injuries.

First claim

What is claimed is:

1. A method of transplanting swine cells, tissue, or organ to a human or non-human primate, the method comprising:
transplanting a cell, tissue, or organ from a swine to the human or non-human primate, wherein the swine is produced by Cesarean section, wherein the cell, tissue, or organ to be transplanted is free of porcine cytomegalovirus (pCMV), wherein the human or non-human primate is under a chronic immunosuppressive treatment comprising administration of a corticosteroid, wherein the immunosuppressive treatment is in absence of induction therapy, and wherein the cell, tissue, or organ comprises cells of skin, or a renal tissue.

2. The method of claim 1 , wherein the swine is a swine that expresses a transgene encoding a human MHC class I protein that inhibits recipient NK cell mediated attack; a swine which is homozygous at swine leukocyte antigens (SLA) A, B, C, DR, and DQ, and in which at least 60% of all other genetic loci are homozygous; or a swine in which the normal expression of alpha(1,3) galactosyltransferase is prevented in at least one organ of tissue type.

3. The method of claim 1 , wherein the swine is a miniature swine.

4. The method of claim 1 , wherein the cell, tissue, or organ is skin or a skin cell.

5. A method of treating a subject who has suffered an injury requiring a skin graft, the method comprising:
transplanting a skin graft from a swine to the subject, wherein the swine is produced by Cesarean section, wherein the skin graft is free of porcine cytomegalovirus (pCMV), wherein the subject is under a chronic immunosuppressive treatment comprising administration of a corticosteroid, wherein the immunosuppressive treatment is in absence of induction therapy.

6. The method of claim 5 , further comprising:
monitoring the skin graft for clinical signs of rejection;
after detection of one or more clinical signs of rejection of the skin graft, removing the skin graft and replacing it with an allogeneic skin graft or an autologous skin graft.

7. The method of claim 6 , wherein the one or more clinical signs of rejection are selected from the group consisting of lack or loss a vascularization; sloughing; white color; darker or pale color compared to normal skin; cooler temperature as compared to normal skin; granulation; crust or scab formation; discharge; and loss or lessening of pliability.

8. The method of claim 5 , wherein the injury is a partial thickness wound or a full thickness wound.

9. The method of claim 8 , wherein the injury comprises burns; avulsed skin; diabetic wounds; and/or venous stasis ulcers.

10. The method of claim 5 , wherein the subject is a human or non-human primate.

11. The method of claim 5 , wherein the skin graft is cryopreserved after harvesting from the swine.

Assignees

• Massachusetts Gen Hospital

Inventors

• Yamada Kazuhiko
• Arn J Scott
• Cetrulo Curtis L
• Sachs David H

Classifications

• A61K35/36

  Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39) · CPC title

• A01K2227/108

  Swine · CPC title

• C12Q1/705

  for herpetoviridae, e.g. herpes simplex, varicella zoster · CPC title

• A61L27/3604

  characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel · CPC title

• A01K67/0271

  Chimeric vertebrates, e.g. comprising exogenous cells · CPC title