University donor cells and related methods

• US 10,391,156 B2
• Filed: 07/12/2017
• Issued: 08/27/2019
• Est. Priority Date: 07/12/2017
• Status: Active Grant

• Current Assignee: Viacyte Incorporated (Vertex Pharmaceuticals Incorporated)
• Original Assignee: Viacyte Incorporated (Vertex Pharmaceuticals Incorporated)
• Inventors: Bhoumik, Anindita, Agulnick, Alan D., D'Amour, Kevin Allen
• Primary Examiner(s): Ton, Thaian N
• Assistant Examiner(s): Montanari, David A.
• Application Number:
  US15/648,337
• Publication Number:
  US 20190015487A1
• Time in Patent Office: 776 Days
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 2501/24 Interferons [IFN]
• CPC Class Codes: C12N 2501/50 Cell markers; Cell surface determinants
• CPC Class Codes: C12N 2501/599 with CD designations not provided for elsewhere
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 2506/02 from embryonic cells
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 5/0606 Pluripotent embryonic cells, e.g. embryonic stem cells [ES] embryonic germ cells C12N5/0611, induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0676 Pancreatic cells
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

1. A human in vitro pancreatic cell population comprising CHGA⁻

, NKX6.1⁺, PDX1⁺ pancreatic progenitor cells, and CHGA⁺ pancreatic endocrine cells,

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, resulting in reduced binding of the NK activating ligand to a NK activating receptor in the human in vitro pancreatic cell population.

2. The in vitro pancreatic cell population of claim 1, wherein the MHC-Class I gene codes for beta-2 microglobulin (B2M).

3. The in vitro pancreatic cell population 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 combinations thereof.

4. The in vitro pancreatic cell population of claim 1, wherein the NK cell activating ligand is ICAM1 and CD58.

5. The in vitro pancreatic cell population of claim 1, wherein the NK cell activating ligand is ICAM1, CD58, CD155, CEACAM1, CADM1, MICA and MICB.

6. The in vitro pancreatic cell population of claim 1, wherein the NK cell activating ligand is ICAM-1, CD58, and CD155.

7. The in vitro pancreatic cell population of claim 1, wherein the pancreatic endoderm cells 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 population.

8. The in vitro cell population of claim 1, wherein the NK cell activating ligand is ICAM1, CD58, CD155, and CADMI.

9. The in vitro cell population of claim 1, wherein the NK cell activating ligand is CD58 and CADM1.

10. The in vitro cell population of claim 1, wherein the NK cell activating ligand is ICAM-1, CADM1, and CD155.