Cytokine receptor genes and the use thereof to enhance therapy

Patent metadata

Field	Value
Publication number	US-11230698-B2
Application number	US-201916448208-A
Country	US
Kind code	B2
Filing date	Jun 21, 2019
Priority date	Jan 23, 2015
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

Cells, such a T-cells, are provided that comprise cytokine receptors having increased activity in response to their ligand. For example, cell can comprise IL-2 and/or IL-15 receptors having increased surface expression or signaling activity. Cells of the embodiments have a significant growth advantage in the presence of cytokines and can be used, e.g., for enhanced adoptive cell transfer therapies.

First claim

What is claimed is:

1. An isolated transgenic human immune cell comprising a recombinant vector comprising a sequence encoding at least one cytokine receptor polypeptide, wherein the cytokine receptor is IL-2.

2. The isolated transgenic human immune cell of claim 1 , wherein the cell is a T-cell, a Natural Killer (NK) cell or a NK T-cell.

3. The isolated transgenic human immune cell of claim 2 , wherein the cell is a T-cell.

4. The isolated transgenic human immune cell of claim 3 , wherein the at least one cytokine receptor comprises IL-2Rα.

5. The isolated transgenic human immune cell of claim 3 , wherein the at least one cytokine receptor comprises IL-2Rβ.

6. The isolated transgenic human immune cell of claim 3 , wherein the at least one cytokine receptor comprises IL-2Rγ.

7. The isolated transgenic human immune cell of claim 2 , wherein the cell is a NK-cell.

8. The isolated transgenic human immune cell of claim 7 , wherein the at least one cytokine receptor comprises IL-2Rα.

9. The isolated transgenic human immune cell of claim 7 , wherein the at least one cytokine receptor comprises IL-2Rβ.

10. The isolated transgenic human immune cell of claim 7 , wherein the at least one cytokine receptor comprises IL-2Rγ.

11. The isolated transgenic human immune cell of claim 1 , wherein the sequence encoding the at least one cytokine receptor polypeptide is operably linked to a heterologous promoter.

12. The isolated transgenic human immune cell of claim 11 , wherein the heterologous promoter is a ligand inducible promoter.

13. The isolated transgenic human immune cell of claim 1 , wherein the cell further comprises a chimeric antigen receptor (CAR).

14. The isolated transgenic human immune cell of claim 13 , wherein the CAR is targeted to cancer cell antigen.

15. A method treating a subject having cancer comprising administering an amount of transgenic human immune cells comprising a recombinant vector comprising a sequence encoding at least one cytokine receptor polypeptide, wherein the cytokine receptor is IL-2 effective to treat said cancer.

16. The method of claim 15 , wherein the transgenic human immune cells comprise T-cells.

17. The method of claim 15 , wherein the transgenic human immune cells comprise NK-cells.

Assignees

• Musc Found For Res Dev

Inventors

• Rubinstein Mark
• Cole David

Classifications

• A61K40/4273

  Glycoprotein 100 [Gp100] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/57

  Skin; melanoma · CPC title

• A61K2239/38

  characterised by the dose, timing or administration schedule · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title