Use of ikk epsilon inhibitors to activate nfat and t cell response

Patent metadata

Field	Value
Publication number	US-2016289684-A1
Application number	US-201415034529-A
Country	US
Kind code	A1
Filing date	Nov 7, 2014
Priority date	Nov 7, 2013
Publication date	Oct 6, 2016
Grant date	—

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

1 . A method for treating a subject suffering from or at risk of developing a disease, the method comprising administering to the subject an IKKε inhibitor.

2 . The method of claim 1 , wherein the disease comprises an infectious disease or cancer.

3 . The method of claim 2 , wherein the disease comprises a viral infection.

4 . The method of any one of the preceding claims, wherein the IKKε inhibitor comprises amlexanox, an inhibitory RNA, an antibody, or a combination thereof.

5 . The method of claim 4 , wherein the inhibitory RNA targets IKKε.

6 . The method of claim 4 or 5 , wherein the inhibitory RNA comprises a shRNA.

7 . The method of claim 6 , wherein the shRNA comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 or SEQ ID NO: 2.

8 . The method of any one of the preceding claims, wherein the IKKε inhibitor increases NFAT activation relative to a control.

9 . The method of any one of the preceding claims, wherein the IKKε inhibitor increases T cell response relative to a control.

10 . The method of claim 9 , wherein CD8 T cell response is increased relative to a control.

11 . The method of claim 9 , wherein the infectious disease comprises a viral infection and the IKKε inhibitor increases anti-viral T-cell mediated immunity.

12 . The method of claim 9 , wherein the infectious disease comprises a microbial infection and the IKKε inhibitor increases anti-microbial T-cell mediated immunity.

13 . The method of claim 9 , wherein the disease comprises cancer and the IKKε inhibitor increases anti-cancer T-cell mediated immunity.

14 . The method of claim 9 , wherein the T cell response is increased by at least about 2-fold to at least about 10-fold.

15 . A method of increasing NFAT activation in a subject, the method comprising administering to the subject an IKKε inhibitor.

16 . A method of increasing T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor.

17 . A method of increasing NFAT activation and T cell response in a subject, the method comprising administering to the subject an IKKε inhibitor.

18 . The method of any one of claims 15 - 17 , wherein the IKKε inhibitor comprises amlexanox, an inhibitory RNA, an antibody, or a combination thereof.

19 . The method of claim 18 , wherein the inhibitory RNA targets IKKε.

20 . The method of claim 18 or 19 , wherein the inhibitory RNA comprises a shRNA.

21 . The method of claim 20 , wherein the shRNA comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 or SEQ ID NO: 2

22 . The method of any one of claims 15 - 17 , wherein CD8 T cell response is increased relative to a control.

23 . The method of any one of the preceding claims, wherein a therapeutically effective amount of the IKKε inhibitor is administered.

24 . A pharmaceutical composition comprising an shRNA selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, and the combination thereof.

25 . The pharmaceutical composition of claim 24 further comprising a pharmaceutically acceptable carrier.

Assignees

• Univ Southern California

Inventors

• Feng Pinghui
• Zhang Junjie
• Feng Hao

Classifications

• 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

• C12N15/1137 Primary

  against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138) · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · 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

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title