Universal donor cells and related methods

Patent metadata

Field	Value
Publication number	US-12576142-B2
Application number	US-202318472072-A
Country	US
Kind code	B2
Filing date	Sep 21, 2023
Priority date	Jul 12, 2017
Publication date	Mar 17, 2026
Grant date	Mar 17, 2026

Abstract

Disclosed herein are universal donor stem cells and cells derived therefrom and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming allogeneic immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor cells disclosed herein are pancreatic endoderm cells that do not express one or more MHC-Class I cell-surface proteins and whose expression of at least one NK activating ligand is disrupted or inhibited.

First claim

The invention claimed is:

1 . A method of producing insulin in a human subject with type I diabetes, comprising:
transplanting a cell encapsulation device comprising pancreatic endoderm cells (PEC) that are CHGA − , NKX6.1 + , PDX1 + into a location in the human subject, wherein the function of at least one major histocompatibility complex (MHC)-Class I gene and at least one natural killer (NK) cell activating ligand is disrupted or inhibited in the PEC, resulting in reduced binding of the NK activating ligand to a NK activating receptor in PEC, and wherein the PEC mature in the human subject to produce insulin in response to glucose stimulation.

2 . The method of claim 1 , wherein the location is subcutaneous in the human subject.

3 . The method of claim 1 , wherein the cell encapsulation device is perforated.

4 . The method of claim 1 , wherein the PEC further express a protein which when expressed in the presence of a cell death inducing agent, the cell death inducing agent is capable of killing cells in the cell encapsulation device.

5 . The method of claim 4 , wherein the protein is herpes simplex virus thymidine kinase and the cell death inducing agent is ganciclovir.

6 . The method of claim 1 , wherein the MHC-Class I gene codes for beta-2 microglobulin (B2M).

7 . The method of claim 1 , wherein the NK cell activating ligand is Intercellular Adhesion Molecule 1 (ICAM1), CD58, CD155, Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1), Cell Adhesion Molecule 1 (CADM1), MHC-Class I Polypeptide-Related Sequence A (MICA), MHC-Class I Polypeptide-Related Sequence B (MICB), or a combination thereof.

8 . The method of claim 1 , wherein the NK cell activating ligand is ICAM1 and CD58.

9 . The method of claim 1 , wherein the NK cell activating ligand is ICAM1, CD58, CD155, CEACAM1, CADM1, MICA and MICB.

10 . The method of claim 1 , wherein the NK cell activating ligand is ICAM-1, CD58, and CD155.

11 . The method of claim 1 , wherein the NK cell activating ligand is ICAM1, CD58, CD155, and CADM1.

12 . The method of claim 1 , wherein the NK cell activating ligand is CD58 and CADM1.

13 . The method of claim 1 , wherein the NK cell activating ligand is ICAM-1, CADM1, and CD155.

Assignees

• Viacyte Inc

Inventors

• Bhoumik Anindita
• Agulnick Alan D
• D'Amour Kevin Allen

Classifications

• C12N5/0676 Primary

  Pancreatic cells · CPC title

• C12N2501/24

  Interferons [IFN] · CPC title

• C12N2506/02

  from embryonic cells · CPC title

• A61K35/39 Primary

  Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36) · CPC title

• C12N2510/00

  Genetically modified cells · CPC title