Use of IKK epsilon inhibitors to activate NFAT and T cell response

Patent metadata

Field	Value
Publication number	US-10370664-B2
Application number	US-201415034529-A
Country	US
Kind code	B2
Filing date	Nov 7, 2014
Priority date	Nov 7, 2013
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

Disclosed herein are compositions and methods of activating nuclear factor of activated T cells (NFAT) and T cell response by inhibiting IKKε.

First claim

What is claimed is:

1. A method for suppressing, repressing, or ameliorating cancer in a subject, the method comprising administering to the subject an IKKε inhibitor, wherein the IKKε inhibitor comprises a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

2. The method of claim 1 , wherein the IKKε inhibitor increases NFAT activation relative to a control.

3. The method of claim 1 , wherein the IKKε inhibitor increases T cell response relative to a control.

4. The method of claim 3 , wherein CD8 T cell response is increased relative to a control.

5. The method of claim 3 , wherein the IKKε inhibitor increases anti-cancer T-cell mediated immunity.

6. The method of claim 3 , wherein the T cell response is increased by at least about 2-fold to at least about 10-fold.

7. The method of claim 1 , wherein a therapeutically effective amount of the IKKε inhibitor is administered.

8. A method of increasing NFAT activation in a subject, the method comprising administering to the subject an IKKε inhibitor comprising a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

9. A method of increasing NFAT activation in a subject, the method comprising administering to the subject an IKKε inhibitor comprising an inhibitory RNA that targets IKKε, wherein CD8 T cell response is increased relative to a control.

10. The method of claim 9 , wherein the inhibitory RNA comprises a shRNA.

11. A method of increasing T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising an inhibitory RNA that targets IKKε, wherein CD8 T cell response is increased relative to a control.

12. A method of increasing NFAT activation and T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising an inhibitory RNA that targets IKKε, wherein CD8 T cell response is increased relative to a control.

13. A method of increasing T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

14. A method of increasing NFAT activation and T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor comprising a polynucleotide sequence selected from SEQ ID NO:1 or SEQ ID NO: 2.

Assignees

• Univ Southern California

Inventors

• Feng Pinghui
• Zhang Junjie
• Feng Hao

Classifications

• C12N2310/531

  Stem-loop; Hairpin · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/436 Primary

  the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin · CPC title